Advertisement

Biology of Retinoschisin

  • Camasamudram Vijayasarathy
  • Lucia Ziccardi
  • Paul A. SievingEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

There is good evidence that retinoschisin (RS1) is one of the key participants in retinal cell adhesion processes controlling the formation of retinal cell layers and mosaics. Loss-of-function mutations in the X-linked retinoschisis (RS1) gene lead to splitting within the retina, a condition known as the X-linked juvenile retinoschisis (XLRS). XLRS causes impairment of visual activity in young males and frequently progresses to even more severe reduction of both central and peripheral vision with age. This perspective reviews progress in the field of RS1 biology and pathophysiology.

Keywords

X-linked retinoschisis Retinoschisin Discoidin domain Mutations Retina Photoreceptors Bipolar cells Synapse Gene therapy 

References

  1. Bradshaw K, George N, Moore A et al (1999) Mutations of the XLRS1 gene cause abnormalities of photoreceptor as well as inner retinal responses of the ERG. Doc Ophthalmol 98:153–173PubMedCrossRefGoogle Scholar
  2. Galli-Resta L, Leone P, Bottari D et al (2008) The genesis of retinal architecture: an emerging role for mechanical interactions? Prog Retin Eye Res 27:260–283PubMedCrossRefGoogle Scholar
  3. George ND, Yates JR, Moore AT (1996) Clinical features in affected males with X-linked retinoschisis. Arch Ophthalmol 114:274–280PubMedCrossRefGoogle Scholar
  4. Hiriyanna KT, Singh-Parikshak R, Bingham EL et al (2001) Searching for genotype-phenotype correlations in X-linked juvenile retinoschisis. In: New Insights Into Retinal Degenerative Diseases. (Anderson RE LVM, Hollyfield JG, ed), pp 45–53. New York: : Plenum PublishersGoogle Scholar
  5. Jablonski MM, Dalke C, Wang X et al (2005) An ENU-induced mutation in Rs1h causes disruption of retinal structure and function. Mol Vis 11:569–581PubMedGoogle Scholar
  6. Janssen A, Min SH, Molday LL et al (2008) Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse. Mol Ther 16:1010–1017PubMedCrossRefGoogle Scholar
  7. Johnson BA, Ikeda S, Pinto LH, Ikeda A (2006) Reduced synaptic vesicle density and aberrant synaptic localization caused by a splice site mutation in the Rs1h gene. Vis Neurosci 23:887–898PubMedCrossRefGoogle Scholar
  8. Johnson BA, Cole BS, Geisert EE, et al. (2010) Tyrosinase is the modifier of retinoschisis in mice. Genetics 186:1337–1344Google Scholar
  9. Khan NW, Jamison JA, Kemp JA et al (2001) Analysis of photoreceptor function and inner retinal activity in juvenile X-linked retinoschisis. Vision Res 41:3931–3942PubMedCrossRefGoogle Scholar
  10. Kjellstrom S, Bush RA, Zeng Y et al (2007) Retinoschisin gene therapy and natural history in the Rs1h-KO mouse: long-term rescue from retinal degeneration. Invest Ophthalmol Vis Sci 48:3837–3845PubMedCrossRefGoogle Scholar
  11. Kotova S, Vijayasarathy C, Dimitriadis EK et al (2010) Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the presence of Ca2+: an atomic force microscopy study. Biochemistry 49:7023–7032PubMedCrossRefGoogle Scholar
  12. Lesch B, Szabo V, Kanya M et al (2008) Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis. Mol Vis 14:2321–2332PubMedGoogle Scholar
  13. Molday LL, Wu WW, Molday RS (2007) Retinoschisin (RS1), the protein encoded by the X-linked retinoschisis gene, is anchored to the surface of retinal photoreceptor and bipolar cells through its interactions with a Na/K ATPase-SARM1 complex. J Biol Chem 282:32792–32801PubMedCrossRefGoogle Scholar
  14. Molday LL, Hicks D, Sauer CG et al (2001) Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells. Invest Ophthalmol Vis Sci 42:816–825PubMedGoogle Scholar
  15. Mooy CM, Van Den Born LI, Baarsma S et al (2002) Hereditary X-linked juvenile retinoschisis: a review of the role of Muller cells. Arch Ophthalmol 120:979–984PubMedGoogle Scholar
  16. Park TK, Wu Z, Kjellstrom S et al (2009) Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse. Gene Ther 16:916–926PubMedCrossRefGoogle Scholar
  17. Pimenides D, George ND, Yates JR et al (2005) X-linked retinoschisis: clinical phenotype and RS1 genotype in 86 UK patients. J Med Genet 42:e35PubMedCrossRefGoogle Scholar
  18. Reid SN, Yamashita C, Farber DB (2003) Retinoschisin, a photoreceptor-secreted protein, and its interaction with bipolar and muller cells. J Neurosci 23:6030–6040PubMedGoogle Scholar
  19. Rodriguez FJ, Rodriguez A, Mendoza-Londono R et al (2005) X-linked retinoschisis in three females from the same family: a phenotype-genotype correlation. Retina 25:69–74PubMedCrossRefGoogle Scholar
  20. Sauer CG, Gehrig A, Warneke-Wittstock R et al (1997) Positional cloning of the gene associated with X-linked juvenile retinoschisis. Nat Genet 17:164–170PubMedCrossRefGoogle Scholar
  21. Sergeev YV, Caruso RC, Meltzer MR et al (2010) Molecular modeling of retinoschisin with functional analysis of pathogenic mutations from human X-linked retinoschisis. Hum Mol Genet 27:27Google Scholar
  22. Shi L, Jian K, Ko ML et al (2009) Retinoschisin, a new binding partner for L-type voltage-gated calcium channels in the retina. J Biol Chem 284:3966–3975PubMedCrossRefGoogle Scholar
  23. Sikkink SK, Biswas S, Parry NR et al (2007) X-linked retinoschisis: an update. J Med Genet 44:225–232PubMedCrossRefGoogle Scholar
  24. Steiner-Champliaud MF, Sahel J, Hicks D (2006) Retinoschisin forms a multi-molecular complex with extracellular matrix and cytoplasmic proteins: interactions with beta2 laminin and alphaB-crystallin. Mol Vis 12:892–901PubMedGoogle Scholar
  25. Takada Y, Vijayasarathy C, Zeng Y et al (2008) Synaptic pathology in retinoschisis knockout (Rs1-/y) mouse retina and modification by rAAV-Rs1 gene delivery. Invest Ophthalmol Vis Sci 49:3677–3686PubMedCrossRefGoogle Scholar
  26. Takada Y, Fariss RN, Muller M, Bush RA, Rushing EJ, Sieving PA (2006) Retinoschisin expression and localization in rodent and human pineal and consequences of mouse RS1 gene knockout. Mol Vis 12:1108–1116Google Scholar
  27. Takada Y, Fariss RN, Tanikawa A et al (2004) A retinal neuronal developmental wave of retinoschisin expression begins in ganglion cells during layer formation. Invest Ophthalmol Vis Sci 45:3302–3312PubMedCrossRefGoogle Scholar
  28. Tantri A, Vrabec TR, Cu-Unjieng A et al (2004) X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol 49:214–230PubMedCrossRefGoogle Scholar
  29. Vijayasarathy C, Takada Y, Zeng Y et al (2007) Retinoschisin is a peripheral membrane protein with affinity for anionic phospholipids and affected by divalent cations. Invest Ophthalmol Vis Sci 48:991–1000PubMedCrossRefGoogle Scholar
  30. Vijayasarathy C, Gawinowicz MA, Zeng Y et al (2006) Identification and characterization of two mature isoforms of retinoschisin in murine retina. Biochem Biophys Res Commun 349:99–105PubMedCrossRefGoogle Scholar
  31. Vijayasarathy C, Ziccardi L, Zeng Y et al (2009) Null retinoschisin-protein expression from an RS1 c354del1-ins18 mutation causing progressive and severe XLRS in a cross-sectional family study. Invest Ophthalmol Vis Sci 50:5375–5383PubMedCrossRefGoogle Scholar
  32. Vijayasarathy C, Sui R, Zeng Y, et al (2010) Molecular mechanisms leading to null-protein product from retinoschisin (RS1) signal-sequence mutants in X-linked retinoschisis (XLRS) disease. Hum Mutat 31:1251–1260Google Scholar
  33. Wang T, Zhou A, Waters CT, O’Connor E et al (2006) Molecular pathology of X linked retinoschisis: mutations interfere with retinoschisin secretion and oligomerisation. Br J Ophthalmol 90:81–86PubMedCrossRefGoogle Scholar
  34. Weber BH, Schrewe H, Molday LL et al (2002) Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure. Proc Natl Acad Sci USA 99:6222–6227PubMedCrossRefGoogle Scholar
  35. Wu WW, Molday RS (2003) Defective discoidin domain structure, subunit assembly, and endoplasmic reticulum processing of retinoschisin are primary mechanisms responsible for X-linked retinoschisis. J Biol Chem 278:28139–28146PubMedCrossRefGoogle Scholar
  36. Wu WW, Wong JP, Kast J, Molday RS (2005) RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer. J Biol Chem 280:10721–10730PubMedCrossRefGoogle Scholar
  37. Zeng Y, Takada Y, Kjellstrom S et al (2004) RS-1 Gene Delivery to an Adult Rs1h Knockout Mouse Model Restores ERG b-Wave with Reversal of the Electronegative Waveform of X-Linked Retinoschisis. Invest Ophthalmol Vis Sci 45:3279–3285PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Camasamudram Vijayasarathy
    • 1
  • Lucia Ziccardi
    • 2
  • Paul A. Sieving
    • 3
    Email author
  1. 1.Section for Translation Research in Retinal and Macular DegenerationNational Institute on Deafness and Other Communication Disorders, National Institutes of HealthBethesdaUSA
  2. 2.Neurophthalmology UnitFondazione “G.B. Bietti” IRCCSRomeItaly
  3. 3.National Eye Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations