Glaucoma Related Ocular Structure and Function

  • Dao-Yi YuEmail author
  • Stephen J. Cringle
  • William H. Morgan


Glaucoma is an aetiologically complex disorder of optic neuropathies. Stressors related to age and intraocular pressure lead to progressive degeneration of the retinal ganglion cells. Clinically ophthalmic testing has been used to identify and quantify the functional and/or structural defects for diagnosis, assessing progression and therapeutic outcomes of glaucoma.

There are multiple ocular structures, which could involve the causes and consequences of glaucoma at the cellular, molecular and genetic levels associated with functional changes. In this chapter, we would like to describe some ocular structures and functions highly relevant to glaucoma.

No doubt, knowledge and information of retinal ganglion cells are critical for understanding glaucoma. The retinal ganglion cells are specialized projection neurons actively receiving visual signal through their dendrites and transmitting integrated visual information from the retina to the brain. Each subcellular component of the retinal ganglion cell is remarkably different in terms of structure, function and extracellular environment. Simplifying the retinal ganglion cells into a series of compartments, rather than attempting to understand it as a single, homogeneous structure, could be more useful for understanding pathogenic processes involved in optic neuropathies.

To understand the mechanisms of maintaining normal intraocular pressure and pathogenesis of elevated intraocular pressure, the only treatable risk factor, we need to understand aqueous humour formation, aqueous fluid dynamics and outflow pathways. This knowledge and information are fundamentally important for understanding the pathogenesis of glaucoma, particularly primary open angle glaucoma, and therapeutic interventions. The epithelium of the ciliary body, posterior surface of the iris and the lens play a role in aqueous humour production and/or barrier function. Endothelial cells line the inner surface of the cornea, trabecular meshwork, Schlemm’s canal, the collector channels and aqueous vein plexus, and the aqueous vein. This chapter provides updated information about the structure and function of the endothelium and epithelium.


Glaucoma Optic nerve head Retinal ganglion cells Trabecular meshwork Aqueous humour 


  1. 1.
    Quigley HA. Open-Angle Glaucoma. N Engl J Med. 1993;328(15):1097–106.PubMedCrossRefGoogle Scholar
  2. 2.
    Vidal-Sanz M, Salinas-Navarro M, Nadal-Nicolas FM, Alarcon-Martinez L, Valiente-Soriano FJ, de Imperial JM, et al. Understanding glaucomatous damage: anatomical and functional data from ocular hypertensive rodent retinas. Prog Retin Eye Res. 2012;31(1):1–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Hood DC. Improving our understanding, and detection, of glaucomatous damage: An approach based upon optical coherence tomography (OCT). Prog Retin Eye Res. 2017;57:46–75.PubMedCrossRefGoogle Scholar
  4. 4.
    Xin C, Wang RK, Song S, Shen T, Wen J, Martin E, et al. Aqueous outflow regulation: Optical coherence tomography implicates pressure-dependent tissue motion. Exp Eye Res. 2017;158:171–86.PubMedCrossRefGoogle Scholar
  5. 5.
    Toris CB. Aqueous Humor Dynamics I: Measurement Methods and Animal Studies. Curr Top Membr. 2008;62:193–229.CrossRefGoogle Scholar
  6. 6.
    Toris CB, Camras CB. Aqueous Humor Dynamics II Clinical Studies. Curr Top Membr. 2008;62:231–72.CrossRefGoogle Scholar
  7. 7.
    Coca-Prados M, Escribano J. New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland. Prog Retin Eye Res. 2007;26(3):239–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Freddo TF, Bartels SP, Barsotti MF, Kamm RD. The source of proteins in the aqueous humor of the normal rabbit. Invest Ophthalmol Vis Sci. 1990;31(1):125–37.PubMedGoogle Scholar
  9. 9.
    Collins R, Van der Werff TJ. Lecture notes in biomathematics. New York: Springer; 1980. p. 1–94.Google Scholar
  10. 10.
    Barany E, Kinsey VE. Rate of flow of aqueous humor. 1. The rate of disappearance of para-aminohippuric acid, radioactive Rayopake, and radioactive Diodrast from the aqueous humor of rabbits. Am J Ophthalmol. 1949;32(6):177–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Kinsey VE, Barany E. The rate of flow of aqueous humor II. Derivation of rate of flow and its physiologic significance. Am J Ophthalmol. 1949;32:189–202.PubMedCrossRefGoogle Scholar
  12. 12.
    Moses RA. Adler’s physiology of the eye. 5th ed. St. Louis: C.V. Mosby; 1970.Google Scholar
  13. 13.
    Kiel JW, Hollingsworth M, Rao R, Chen M, Reitsamer HA. Ciliary blood flow and aqueous humor production. Prog Retin Eye Res. 2011;30(1):1–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Gabelt BT, Kaufman PL. Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res. 2005;24(5):612–37.PubMedCrossRefGoogle Scholar
  15. 15.
    Yang H, Yu PK, Cringle SJ, Sun X, Yu DY. Quantitative study of the microvasculature and its endothelial cells in the porcine iris. Exp Eye Res. 2015;132C:249–58.CrossRefGoogle Scholar
  16. 16.
    Yang H, Yu PK, Cringle SJ, Sun X, Yu D-Y. Iridal vasculature and the vital roles of the iris. J Nat Sci. 2015;1(8):e157.Google Scholar
  17. 17.
    Yang H, Yu PK, Cringle SJ, Sun X, Yu DY. Intracellular cytoskeleton and junction proteins of endothelial cells in the porcine iris microvasculature. Exp Eye Res. 2015;140:106–16.PubMedCrossRefGoogle Scholar
  18. 18.
    Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye: an atlas and textbook, vol. 1971. Philadelphia: W.B. Saunders Company; 1971.Google Scholar
  19. 19.
    Tousimis AJ, Fine BS. Ultrastructure of the iris: the intercellular stromal components. Arch Ophthalmol. 1959;62:974–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Vrabec F. The anterior superficial endothelium of the human iris. Ophthalmologica. 1952;123(1):20–30.PubMedCrossRefGoogle Scholar
  21. 21.
    Freddo TF. Ultrastructure of the iris. Microsc Res Tech. 1996;33(5):369–89.PubMedCrossRefGoogle Scholar
  22. 22.
    Oyster CW. The human eye, structure and function. Ophthalmic Physiol Opt. 2000;20(4):349–50.CrossRefGoogle Scholar
  23. 23.
    Tasman W, Jaeger EA, editors. Duane’s clinical ophthalmology on CD-ROM. Philadelphia: Lippincott Williams & Wilkins; 2005.Google Scholar
  24. 24.
    Raviola G, Butler JM. Morphological evidence for the transfer of anionic macromolecules from the interior of the eye to the blood stream. Curr Eye Res. 1985;4(4):503–16.PubMedCrossRefGoogle Scholar
  25. 25.
    Freddo TF. A contemporary concept of the blood-aqueous barrier. Prog Retin Eye Res. 2013;32:181–95.PubMedCrossRefGoogle Scholar
  26. 26.
    Vanderkooi JM, Erecinska M, Silver IA. Oxygen in mammalian tissue-methods of measurement and affinities of various reactions. Am J Physiol. 1991;260(6):C1131–C50.PubMedCrossRefGoogle Scholar
  27. 27.
    Abu-Amero KK, Morales J, Bosley TM. Mitochondrial abnormalities in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006;47(6):2533–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004;10(Suppl):S18–25.PubMedCrossRefGoogle Scholar
  29. 29.
    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335–44.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Leung BK, Bonanno JA, Radke CJ. Oxygen-deficient metabolism and corneal edema. Prog Retin Eye Res. 2011;30(6):471–92.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Chhabra M, Prausnitz JM, Radke CJ. Modeling corneal metabolism and oxygen transport during contact lens wear. Optom Vis Sci. 2009;86(5):454–66.PubMedCrossRefGoogle Scholar
  32. 32.
    Chhabra M, Prausnitz JM, Radke CJ. Diffusion and Monod kinetics to determine in vivo human corneal oxygen-consumption rate during soft contact-lens wear. J Biomed Mater Res B Appl Biomater. 2009;90(1):202–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Alvord LA, Hall WJ, Keyes LD, Morgan CF, Winterton LC. Corneal oxygen distribution with contact lens wear. Cornea. 2007;26(6):654–64.PubMedCrossRefGoogle Scholar
  34. 34.
    Shui YB, Fu JJ, Garcia C, Dattilo LK, Rajagopal R, McMillan S, et al. Oxygen distribution in the rabbit eye and oxygen consumption by the lens. Invest Ophthalmol Vis Sci. 2006;47(4):1571–80.PubMedCrossRefGoogle Scholar
  35. 35.
    Bonanno JA, Stickel T, Nguyen T, Biehl T, Carter D, Benjamin WJ, et al. Estimation of human corneal oxygen consumption by noninvasive measurement of tear oxygen tension while wearing hydrogel lenses. Invest Ophthalmol Vis Sci. 2002;43(2):371–6.PubMedGoogle Scholar
  36. 36.
    Stefansson E, Foulks GN, Hamilton RC. The effect of corneal contact lenses on the oxygen tension in the anterior chamber of the rabbit eye. Invest Ophthalmol Vis Sci. 1987;28(10):1716–9.PubMedGoogle Scholar
  37. 37.
    Siegfried CJ, Shui YB, Holekamp NM, Bai F, Beebe DC. Oxygen distribution in the human eye: relevance to the etiology of open-angle glaucoma after vitrectomy. Invest Ophthalmol Vis Sci. 2010;51(11):5731–8.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Chang S. LXII Edward Jackson lecture: open angle glaucoma after vitrectomy. Am J Ophthalmol. 2006;141(6):1033–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Luk FO, Kwok AK, Lai TY, Lam DS. Presence of crystalline lens as a protective factor for the late development of open angle glaucoma after vitrectomy. Retina. 2009;29(2):218–24.PubMedCrossRefGoogle Scholar
  40. 40.
    Holekamp NM, Shui YB, Beebe DC. Vitrectomy surgery increases oxygen exposure to the lens: a possible mechanism for nuclear cataract formation. Am J Ophthalmol. 2005;139(2):302–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Barbazetto IA, Liang J, Chang S, Zheng L, Spector A, Dillon JP. Oxygen tension in the rabbit lens and vitreous before and after vitrectomy. Exp Eye Res. 2004;78(5):917–24.PubMedCrossRefGoogle Scholar
  42. 42.
    McNulty R, Wang H, Mathie RT, Ortwerth B, Truscott RJW, Bassnett S. regulation of tissue oxygen levels in the mammalian lens. J Physiol. 2004;559(3):883–98.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Edelhauser HF. Cornea and lens oxygen consumption in rabbit and trout: a comparative study. Exp Eye Res. 1974;19:317–22.PubMedCrossRefGoogle Scholar
  44. 44.
    Freeman RD. Oxygen consumption by the component layers of the cornea. J Physiol. 1972;225(1):15–32.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Izzotti A, Longobardi M, Cartiglia C, Sacca SC. Mitochondrial damage in the trabecular meshwork occurs only in primary open-angle glaucoma and in pseudoexfoliative glaucoma. PLoS One. 2011;6(1):e14567.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Yu DY, Morgan WH, Sun X, Su EN, Cringle SJ, Yu PK, et al. The critical role of the conjunctiva in glaucoma filtration surgery. Prog Retin Eye Res. 2009;28(5):303–28.PubMedCrossRefGoogle Scholar
  47. 47.
    Niederkorn JY. Mechanisms of immune privilege in the eye and hair follicle. J Investig Dermatol Symp Proc. 2003;8:168–72.PubMedCrossRefGoogle Scholar
  48. 48.
    Dermietzel R, Spray DC, Nedergaard M. The blood-brain barrier: an integrated concept. In: Dermietzel R, Spray DC, Nedergaard M, editors. Blood-brain interfaces: from ontogeny to artificial barriers. Weinheim: Wiley; 2006.CrossRefGoogle Scholar
  49. 49.
    Streilein JW. Immunological non-responsiveness and acquisition of tolerance in relation to immune privilege in the eye. Eye. 1995;9(Pt 2):236–40.PubMedCrossRefGoogle Scholar
  50. 50.
    Streilein JW. Ocular immune priviledge: therapeutic opportunities from an experiment of nature. Nat Rev Immunol. 2003;3(November):879–89.PubMedCrossRefGoogle Scholar
  51. 51.
    Fautsch MP, Johnson DH, Group tSAPRIW. Aqueous humor outflow: what do we know? where will it lead us? Biophys J. 2004;87:2828–37.CrossRefGoogle Scholar
  52. 52.
    Bill A. The drainage of aqueous humor. Investig Ophthalmol. 1975;14(1):1–3.Google Scholar
  53. 53.
    Stamer WD. The biology of Schlemm’s canal. Amsterdam: Elsevier Ltd.; 2010.CrossRefGoogle Scholar
  54. 54.
    Rohen JW, Schachtschabel DO, Berghoff K. Histoautoradiographic and biochemical studies on human and monkey trabecular meshwork and ciliary body in short-term explant culture. Graefes Arch Clin Exp Ophthalmol. 1984;221:199–206.PubMedCrossRefGoogle Scholar
  55. 55.
    Rohen JW, van der Zypen E. The phagocytic activity of the trabecular meshwork endothelium: an elecron microscopic study of the vervet (Cercopithecus aethiops). Graefes Arch Clin Exp Ophthalmol. 1968;175:143.CrossRefGoogle Scholar
  56. 56.
    Broadway DC, Grierson I, Hitchings RA. Local effects of previous conjunctival incisional surgery and the subsequent outcome of filtration surgery. Am J Ophthalmol. 1998;125:805–18.PubMedCrossRefGoogle Scholar
  57. 57.
    Grierson I, Lee WR. Further observations on the process of haemophagocytosis in the human outflow system. Graefes Arch Clin Exp Ophthalmol. 1978;208:49–64.CrossRefGoogle Scholar
  58. 58.
    Grierson I, Lee WR. Erythrocyte phagocytosis in the human trabecular meshwork. Br J Ophthalmol. 1973;57:400–15.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Lee WR, Grierson I, McMenamin PG. The morphological response of the primate outflow system to changes in pressure and flow. In: Lutjen-Drecoll E, editor. Basic aspects of glaucoma research. Stuttgart: Schattauert Verlag; 1982.Google Scholar
  60. 60.
    Lutjen-Drecoll E, Futa R, Rohen JW. Ultrahistochemical studies on tangential sections of the trabecular meshwork in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 1981;21:563–73.PubMedGoogle Scholar
  61. 61.
    Quigley HA, Addicks EM. Chronic experimenal glaucoma in pimates. I. Production of elevated intraocular pressure by anterior chamber injection of autologous ghost red blood cells. Invest Ophthalmol Vis Sci. 1980;19:126–36.PubMedGoogle Scholar
  62. 62.
    Shabo AL, Maxwell DS. Observations on the fate of blood in the anterior chamber: a light and electron microscopic study of the monkey trabecular meshwork. Am J Ophthalmol. 1972;73:25–36.PubMedCrossRefGoogle Scholar
  63. 63.
    Sherwood M, Richardson TM. Kinetics of the phagocytic process in the trabecular meshwork of cats and monkeys. Invest Ophthalmol Vis Sci. 1981;20(Suppl):65.Google Scholar
  64. 64.
    Vegge T. The fine structure of the trabeculum cribriforme and the inner wall of Schlemm’s canal in the normal human eye. Z Zellforsch. 1967;77:267–81.PubMedCrossRefGoogle Scholar
  65. 65.
    Yu DY, Yu PK, Cringle SJ, Kang MH, Su EN. Functional and morphological characteristics of the retinal and choroidal vasculature. Prog Retin Eye Res. 2014;40:53–93.PubMedCrossRefGoogle Scholar
  66. 66.
    Ramos RF, Hoying JB, Witte MH, Daniel Stamer W. Schlemm’s canal endothelia, lymphatic, or blood vasculature? J Glaucoma. 2007;16(4):391–405.PubMedCrossRefGoogle Scholar
  67. 67.
    Alvarado JA, Betanzos A, Franse-Carman L, Chen J, Gonzalez-Mariscal L. Endothelia of Schlemm’s canal and trabecular meshwork: distinct molecular, functional, and anatomic features. Am J Physiol Cell Physiol. 2004;286(3):C621–34.PubMedCrossRefGoogle Scholar
  68. 68.
    Ethier CR, Read AT, Chan D. Biomechanics of Schlemm’s canal endothelial cells: influence on F-actin architecture. Biophys J. 2004;87(4):2828–37.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Ashton N. Anatomical study of Schlemm’s canal and aqueous veins by means of neoprene casts. Part I. Aqueous veins. Br J Ophthalmol. 1951;35:291–303.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Dvorak-Theobald G. Schlemm’s canal: its anastomoses and anatomic relations. Trans Am Ophthalmol Soc. 1934;32:574–95.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Krohn J, Rodahl E. Expression of 5′-nucleotidase and alkaline phosphatase in human aqueous drainage channels. Acta Ophthalmol Scand. 2002;80(6):642–51.PubMedCrossRefGoogle Scholar
  72. 72.
    Bentley MD, Hann CR, Fautsch MP. Anatomical variation of human collector channel orifices. Invest Ophthalmol Vis Sci. 2016;57(3):1153–9.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Dvorak-Theobald G, Kirk HQ. Aqueous pathways in some cases of glaucoma. Trans Am Ophthalmol Soc. 1955;53:301–19.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Dvorak-Theobald G. Further studies on the canal of Schlemm: its anastomoses and anatomic relations. Am J Ophthalmol. 1955;39:65–89.PubMedCrossRefGoogle Scholar
  75. 75.
    Ascher KW. Aqueous veins: preliminary note. Am J Ophthalmol. 1942;25:33–8.Google Scholar
  76. 76.
    Kagemann L, Wollstein G, Ishikawa H, Sigal IA, Folio LS, Xu J, et al. 3D visualization of aqueous humor outflow structures in-situ in humans. Exp Eye Res. 2011;93(3):308–15.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Ethier CR. The inner wall of Schlemm’s canal. Exp Eye Res. 2002;74(2):161–72.PubMedCrossRefGoogle Scholar
  78. 78.
    Johnson M, Erickson K. Mechanisms and routes of aqueous humor drainage. Aqueous humor and the dynamics of its flow. 2006. p. 2577–95.Google Scholar
  79. 79.
    Johnstone M, Martin E, Jamil A. Pulsatile flow into the aqueous veins: manifestations in normal and glaucomatous eyes. Exp Eye Res. 2011;92(5):318–27.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res. 1971;12:275–81.PubMedCrossRefGoogle Scholar
  81. 81.
    Bill A. Aqueous humor dynamics in monkeys (Macaca irus and Cercopithecus ethiops). Exp Eye Res. 1971;11:195–206.PubMedCrossRefGoogle Scholar
  82. 82.
    Bill A. The routes for bulk drainage of aqueous humour in the vervet monkey (Cercopithecus ethiops). Exp Eye Res. 1966;5:55–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Bill A. Conventional and Uveo-scleral drainage of aqueoue humour in the Cynomolgus monkey (Macaca irus) at normal and high intraocular pressures. Exp Eye Res. 1966;5:45–54.PubMedCrossRefGoogle Scholar
  84. 84.
    Bill A, Hellsing K. Production and drainage of aqueous humor in the cynomolgus monkey (Macaca irus). Investig Ophthalmol. 1965;4(5):920–6.Google Scholar
  85. 85.
    Bill A. The aqueous humor drainage mechanism in the cynomolgus monkey (Macaca irus) with evidence for unconventional routes. Investig Ophthalmol. 1965;4:911.Google Scholar
  86. 86.
    Alm A, Nilsson SF. Uveoscleral outflow--a review. Exp Eye Res. 2009;88(4):760–8.CrossRefGoogle Scholar
  87. 87.
    Bill A. Uveoscleral drainage of aqueous humor: physiology and pharmacology. Prog Clin Biol Res. 1989;312:417–27.PubMedGoogle Scholar
  88. 88.
    London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol. 2013;9(1):44–53.PubMedCrossRefGoogle Scholar
  89. 89.
    Yu DY, Cringle SJ, Balaratnasingam C, Morgan WH, Yu PK, Su EN. Retinal ganglion cells: energetics, compartmentation, axonal transport, cytoskeletons and vulnerability. Prog Retin Eye Res. 2013;36:217–46.PubMedCrossRefGoogle Scholar
  90. 90.
    Hein K, Bäher M. Optic nerve: optic neuritis. In: Dartt DA, editor. Encyclopedia of the eye. Oxford: Academic; 2010. p. 205–9.CrossRefGoogle Scholar
  91. 91.
    Friede RL. The relationship of body size, nerve cell size, axon length, and glial density in the cerebellum. Proc Natl Acad Sci U S A. 1963;49(2):187–93.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Friedrich P. Dynamic compartmentation in soluble multienzyme systems. In: Welch GR, editor. Organized multienzyme systems: catalytic properties. Biotechnology and applied biochemistry series. Orlando: Academic; 1985. p. 141–76.CrossRefGoogle Scholar
  93. 93.
    Kellermayer M, Ludany A, Jobst K, Szucs G, Trombitas K, Hazlewood CF. Cocompartmentation of proteins and K+ within the living cell. Proc Natl Acad Sci U S A. 1986;83(4):1011–5.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Bereiter-Hahn J, Vöth M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion and fission of mitochondria. Microsc Res Tech. 1994;27:198–219.PubMedCrossRefGoogle Scholar
  95. 95.
    Whitmore AV, Libby RT, John SW. Glaucoma: thinking in new ways-a role for autonomous axonal self-destruction and other compartmentalised processes? Prog Retin Eye Res. 2005;24(6):639–62.PubMedCrossRefGoogle Scholar
  96. 96.
    Dubbin PN, Cody SH, Williams DA. Intracellular pH mapping with SNARF-1 and confocal microscopy. II: pH gradients within single cultured cells. Micron. 1993;24(6):581–6.CrossRefGoogle Scholar
  97. 97.
    Iturriaga R, Rumsey WL, Lahiri S, Spergel D, Wilson DF. Intracellular pH and oxygen chemoreception in the cat carotid body in vitro. J Appl Physiol. 1992;72(6):2259–66.PubMedCrossRefGoogle Scholar
  98. 98.
    Clegg JS. Intracellular water and the cytomatrix: some methods of study and current views. J Cell Biol. 1984;99(1 Pt 2):167s–71s.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Clegg JS. On the internal environment of animal cells. In: Jones DP, editor. Microcompartmentation. Boca Raton: CRC Press; 1988. p. 1–16.Google Scholar
  100. 100.
    Jones DP, Aw TY. Mitochondrial distribution and O2 gradients in mammalian cells. In: Jones DP, editor. Microcompartmentation. Boca Raton: CRC Press; 1988. p. 37–54.Google Scholar
  101. 101.
    Minaschek G, Groschel-Stewart U, Blum S, Bereiter-Hahn J. Microcompartmentation of glycolytic enzymes in cultured cells. Eur J Cell Biol. 1992;58(2):418–28.PubMedGoogle Scholar
  102. 102.
    Wang JT, Medress ZA, Barres BA. Axon degeneration: molecular mechanisms of a self-destruction pathway. J Cell Biol. 2012;196(1):7–18.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Shetty PK, Galeffi F, Turner DA. Cellular links between neuronal activity and energy homeostasis. Front Pharmacol. 2012;3:43.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Allen NJ, Barres BA. Glia and synapse formation: an overview. In: Editor-in-Chief:-á-álarry RS, editor. Encyclopedia of neuroscience. Oxford: Academic; 2009. p. 731–6.CrossRefGoogle Scholar
  105. 105.
    Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232–43.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Wollner DA, Catterall WA. Localization of sodium channels in axon hillocks and initial segments of retinal ganglion cells. Proc Natl Acad Sci U S A. 1986;83(21):8424–8.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Tan PE, Yu PK, Balaratnasingam C, Cringle SJ, Morgan WH, McAllister IL, et al. Quantitative confocal imaging of the retinal microvasculature in the human retina. Invest Ophthalmol Vis Sci. 2012;53(9):5728–36.PubMedCrossRefGoogle Scholar
  108. 108.
    Yu DY, Cringle SJ, Alder VA, Su EN. Intraretinal oxygen distribution in rats as a function of systemic blood pressure. Am J Phys. 1994;267(6 Pt 2):H2498–H507.Google Scholar
  109. 109.
    Yu DY, Cringle SJ, Yu PK, Su EN. Intraretinal oxygen distribution and consumption during retinal artery occlusion and graded hyperoxic ventilation in the rat. Invest Ophthalmol Vis Sci. 2007;48(5):2290–6.PubMedCrossRefGoogle Scholar
  110. 110.
    Yu DY, Cringle SJ. Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog Retin Eye Res. 2001;20(2):175–208.PubMedCrossRefGoogle Scholar
  111. 111.
    Morgan JE. Retina ganglion cell degeneration in glaucoma: an opportunity missed? a review. Clin Exp Ophthalmol. 2012;40(4):364–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131(6):1164–78.PubMedCrossRefGoogle Scholar
  113. 113.
    Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res. 2004;23(1):91–147.PubMedCrossRefGoogle Scholar
  114. 114.
    Kuwabara T, Cogan DG. Retinal glycogen. Arch Ophthalmol. 1961;66:680–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Li ZW, Liu S, Weinreb RN, Lindsey JD, Yu M, Liu L, et al. Tracking dendritic shrinkage of retinal ganglion cells after acute elevation of intraocular pressure. Invest Ophthalmol Vis Sci. 2011;52(10):7205–12.PubMedCrossRefGoogle Scholar
  116. 116.
    Munemasa Y, Kitaoka Y. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection. Front Cell Neurosci. 2012;6:60.PubMedGoogle Scholar
  117. 117.
    Chan G, Balaratnasingam C, Yu PK, Morgan WH, McAllister IL, Cringle SJ, et al. Quantitative morphometry of perifoveal capillary networks in the human retina. Invest Ophthalmol Vis Sci. 2012;53(9):5502–14.PubMedCrossRefGoogle Scholar
  118. 118.
    Rolfe DFS, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev. 1997;77(3):731–58.PubMedCrossRefGoogle Scholar
  119. 119.
    Laughlin SB. Energy as a constraint on the coding and processing of sensory information. Curr Opin Neurobiol. 2001;11(4):475–80.PubMedCrossRefGoogle Scholar
  120. 120.
    Laughlin SB, Weckström M. Fast and slow photoreceptors - a comparative study of the functional diversity of coding and conductances in the Diptera. J Comp Physiol A. 1993;172:593–609.CrossRefGoogle Scholar
  121. 121.
    Zador A. Impact of synaptic unreliability on the information transmitted by spiking neurons. J Neurophysiol. 1998;79(3):1219–29.PubMedCrossRefGoogle Scholar
  122. 122.
    Andrews RM, Griffiths PG, Johnson MA, Turnbull DM. Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina. Br J Ophthalmol. 1999;83(2):231–5.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Wang L, Dong J, Cull G, Fortune B, Cioffi GA. Varicosities of intraretinal ganglion cell axons in human and nonhuman primates. Invest Ophthalmol Vis Sci. 2003;44(1):2–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Osborne NN. Mitochondria: their role in ganglion cell death and survival in primary open angle glaucoma. Exp Eye Res. 2010;90(6):750–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Balaratnasingam C, Morgan WH, Bass L, Kang M, Cringle SJ, Yu DY. Time-dependent effects of focal retinal ischemia on axonal cytoskeleton proteins. Invest Ophthalmol Vis Sci. 2010;51(6):3019–28.PubMedCrossRefGoogle Scholar
  126. 126.
    Morgan WH, Yu D-Y, Cooper RL, Cringle SJ, Alder VA. The influence of cerebrospinal fluid pressure upon the lamina cribrosa tissue pressure gradient - correspondence. Investig Ophthalmol Vis Sci. 1995;36:2163–4.Google Scholar
  127. 127.
    Morgan WH, Yu D-Y, Cooper RL, Alder VA, Cringle SJ, Constable IJ. The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient. Investig Ophthalmol Vis Sci. 1995;36(6):1163–72.Google Scholar
  128. 128.
    Morgan WH, Yu D-Y, Alder VA, Cringle SJ, Cooper RL, House PH, et al. The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure. Investig Ophthalmol Vis Sci. 1998;39(8):1419–28.Google Scholar
  129. 129.
    Balaratnasingam C, Morgan WH, Johnstone V, Pandav SS, Cringle SJ, Yu DY. Histomorphometric measurements in human and dog optic nerve and an estimation of optic nerve pressure gradients in human. Exp Eye Res. 2009;89(5):618–28.PubMedCrossRefGoogle Scholar
  130. 130.
    Ochs S. Energy metabolism and supply of -P to the fast axoplasmic transport mechanism in nerve. Fed Proc. 1974;33:1049–58.Google Scholar
  131. 131.
    Hahnenberger RW. Effect of a pressure barrier on retrograde axoplasmic transport in vitro. A study in the motor neurons of the rabbit vagus. Acta Physiol Scand. 1980;108(2):133–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Hayreh SS, Bill A, Sperber GO. Effects of high intraocular pressure on the glucose metabolism in the retina and optic nerve in old atherosclerotic monkeys. Graefes Arch Clin Exp Ophthalmol. 1994;232(12):745–52.PubMedCrossRefGoogle Scholar
  133. 133.
    Rydevik B, Lundborg G, Bagge U. Effects of graded compression on intraneural blood blow. An in vivo study on rabbit tibial nerve. J Hand Surg Am. 1981;6(1):3–12.PubMedCrossRefGoogle Scholar
  134. 134.
    Rodriguez-Tebar A, Jeffrey PL, Thoenen H, Barde YA. The survival of chick retinal ganglion cells in response to brain-derived neurotrophic factor depends on their embryonic age. Dev Biol. 1989;136(2):296–303.PubMedCrossRefGoogle Scholar
  135. 135.
    Mansour-Robaey S, Clarke DB, Wang YC, Bray GM, Aguayo AJ. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A. 1994;91(5):1632–6.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Hayreh SS. Ischemic optic neuropathy. In: Dartt DA, editor. Encyclopedia of the eye. Oxford: Academic; 2010. p. 487–99.CrossRefGoogle Scholar
  137. 137.
    Erdogmus S, Govsa F. Anatomic characteristics of the ophthalmic and posterior ciliary arteries. J Neuroophthalmol. 2008;28:320–40.PubMedCrossRefGoogle Scholar
  138. 138.
    Mackenzie PJ, Cioffi GA. Vascular anatomy of the optic nerve head. Can J Ophthalmol. 2008;43(3):308–12.PubMedCrossRefGoogle Scholar
  139. 139.
    Waxman SG, Kocsis JD, Stys PK. The axon. Structure, function and pathophysiology, vol. 1995. New York: Oxford University Press; 1995.CrossRefGoogle Scholar
  140. 140.
    Sadun A. Acquired mitochondrial impairment as a cause of optic nerve disease. Trans Am Ophthalmol Soc. 1998;96:881–923.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Wong-Riley MT. Energy metabolism of the visual system. Eye Brain. 2010;2:99–116.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Sun X, Dai Y, Chen Y, Yu DY, Cringle SJ, Chen J, et al. Primary angle closure glaucoma: what we know and what we don’t know. Prog Retin Eye Res. 2016;57:26–45.PubMedCrossRefGoogle Scholar
  143. 143.
    Kaufman PL, Alm A, editors. Adler’s physiology of the eye: clinical application. St. Louis: Mosby; 2003.Google Scholar
  144. 144.
    Collins R, Van der Werff TJ. Mathematical models of the dynamics of the human eye. In: Levin S, editor. Lecture notes in biomathematics. Berlin: Springer; 1980.Google Scholar
  145. 145.
    Bill A, Sperber GO. Control of retinal and choroidal blood flow. Eye. 1990;4:319–25.PubMedCrossRefGoogle Scholar
  146. 146.
    Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res. 2010;29(2):144–68.PubMedCrossRefGoogle Scholar
  147. 147.
    Alm A, Bill A. Ocular circulation. In: Hart WM, Moses RA, editors. Adler’s physiology of the eye: clinical application. 8th ed. St Louis: Mosby; 1987. p. 183–99.Google Scholar
  148. 148.
    Smith EL, Hill RA, Lehman IR, Lefkowitz RJ, Handler P, White A. Principles of biochemistry: mammalian biochemistry, vol. 1985. 7th ed. Singapore: McGraw-Hill Book Company; 1985.Google Scholar
  149. 149.
    Yu D-Y, Cringle SJ. Outer retinal anoxia during dark adaptation is not a general property of mammalian retinas. Comp Biochem Physiol. 2002;132:47–52.CrossRefGoogle Scholar
  150. 150.
    Potter JW, Vandervort RS, Thallemer JM. The clinical significance of the vortex veins. J Am Optom Assoc. 1984;55(11):822–4.PubMedGoogle Scholar
  151. 151.
    Yu PK, Tan PE, Cringle SJ, McAllister IL, Yu DY. Phenotypic heterogeneity in the endothelium of the human vortex vein system. Exp Eye Res. 2013;115C:144–52.CrossRefGoogle Scholar
  152. 152.
    Tan PE, Yu PK, Cringle SJ, Morgan WH, Yu DY. Regional heterogeneity of endothelial cells in the porcine vortex vein system. Microvasc Res. 2013;89:70–9.PubMedCrossRefGoogle Scholar
  153. 153.
    Yu PK, Cringle SJ, Yu DY. Quantitative study of age-related endothelial phenotype change in the human vortex vein system. Microvasc Res. 2014;94:64–72.PubMedCrossRefGoogle Scholar
  154. 154.
    Quigley HA. Angle-closure glaucoma-simpler answers to complex mechanisms: LXVI Edward Jackson memorial lecture. Am J Ophthalmol. 2009;148(5):657–69.PubMedCrossRefGoogle Scholar
  155. 155.
    Mak H, Xu G, Leung CK. Imaging the iris with swept-source optical coherence tomography: relationship between iris volume and primary angle closure. Ophthalmology. 2013;120(12):2517–24.PubMedCrossRefGoogle Scholar
  156. 156.
    Seager FE, Jefferys JL, Quigley HA. Comparison of dynamic changes in anterior ocular structures examined with anterior segment optical coherence tomography in a cohort of various origins. Invest Ophthalmol Vis Sci. 2014;55(3):1672–83.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Aptel F, Chiquet C, Beccat S, Denis P. Biometric evaluation of anterior chamber changes after physiologic pupil dilation using Pentacam and anterior segment optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53(7):4005–10.PubMedCrossRefGoogle Scholar
  158. 158.
    Baskaran M, Ho SW, Tun TA, How AC, Perera SA, Friedman DS, et al. Assessment of circumferential angle-closure by the iris-trabecular contact index with swept-source optical coherence tomography. Ophthalmology. 2013;120(11):2226–31.PubMedCrossRefGoogle Scholar
  159. 159.
    Quigley HA, Silver DM, Friedman DS, He M, Plyler RJ, Eberhart CG, et al. Iris cross-sectional area decreases with pupil dilation and its dynamic behavior is a risk factor in angle closure. J Glaucoma. 2009;18(3):173–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Dao-Yi Yu
    • 1
    • 2
    Email author
  • Stephen J. Cringle
    • 1
    • 2
  • William H. Morgan
    • 1
    • 2
  1. 1.Centre for Ophthalmology and Visual ScienceThe University of Western AustraliaNedlandsAustralia
  2. 2.Lions Eye InstituteThe University of Western AustraliaNedlandsAustralia

Personalised recommendations