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Introduction: Overview of the Human Eye, Mammalian Retina, and the Retinoid Visual Cycle

  • Christopher L. CioffiEmail author
Part of the Topics in Medicinal Chemistry book series


The human eye is a part of the sensory nervous system and is the organ responsible for conscious light perception and vision. Its intricate and complex anatomy has evolved to effectively focus incoming light from the surrounding environment and to harness its energy by efficiently utilizing the physicochemical properties of retinoids. This remarkable organ is capable of phototransduction, which involves the conversion of photon energy into an integrated neural signal that propagates through the optic nerve as an action potential to the visual cortex of the brain. There, the neural signal is processed to give rise to color differentiation, brightness perception, contrast, and depth perception. Loss of visual acuity or blindness presents a significant negative impact on quality of life. Irreversible blindness affects nearly 60 million individuals worldwide, with the leading causes including age-related macular degeneration, glaucoma, and retinal vascular disease. In this chapter, we will provide basic background information of the human eye and retina required for readers unfamiliar with the field of ophthalmic drug discovery. The purpose of this chapter is to help facilitate a thorough understanding of the subsequent chapters of this volume that focus on key ophthalmic diseases, recent developments in drug discovery efforts toward treating these diseases, and the challenges faced in the delivery of drugs to their ocular targets. Thus, this chapter will provide a general overview that begins with the gross anatomical features of the human eye followed by a description of the histology of the mammalian retina. We will next provide morphological and functional details concerning the various cell types that comprise the many layers of the retina, and we will conclude by describing the series of reactions that constitute the visual retinoid cycle and the various key proteins that facilitate it.


Anterior chamber Anterior segment Choroid Macula Photoreceptors Phototransduction Posterior chamber Posterior segment Retina Retinal pigment epithelium (RPE) Retinoids Visual cycle 



α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Basal bodies


Blood-brain barrier


Blood-retinal barrier


Connecting cilium


Complement factor H


Cyclic guanosine monophosphate


Cone inner segment


Cyclic nucleotide-gated


Central nervous system


Ciliary neurotrophic factor


Cone outer segment


Cellular retinaldehyde-binding protein


Cellular retinol-binding protein


Endoplasmic reticulum




γ-Aminobutyric acid


Guanosine diphosphate


G protein-coupled receptor


Guanosine triphosphate


Insulin-like growth factor-I


Inner limiting membrane




Interphotoreceptor matrix


Intracellular retinol-binding protein


Inner segment


Lens epithelium-derived growth factor


Lateral geniculate nucleus


Lecithin-retinol acyltransferase


Metabotropic glutamate 6


Nonpigmented epithelial cells


Outer limiting membrane


Outer nuclear layer


Outer segment




Platelet-derived growth factor




Pigmented epithelial cells


Photoreceptor outer segment


Retinol-binding protein 4


Retinol dehydrogenase 11


Retinol dehydrogenase 5


Retinol dehydrogenase 8


Retinal ganglion cell


Rod inner segment


Rod outer segment


Retinal pigment epithelium


Stimulated by retinoic acid 6 protein


Transforming growth factor-β


Transmembrane domain





We thank our funding agency [National Institutes of Health, National Eye Institute grant R01 EY028549-01] for their continued support of our ongoing drug discovery research toward the identification of bispecific antagonists of RBP4 and kinetic stabilizers of TTR tetramers. These agents are under investigation for their potential to treat atrophic age-related macular degeneration while preventing TTR amyloid fibril formation and age-related amyloid disease such as senile systemic amyloidosis.

Compliance with Ethical Standards

This manuscript is a review of previously published accounts, as such no animal or human studies were performed.

Conflict of Interest

The author declares no conflict of interest or competing financial interest.


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Basic and Clinical SciencesAlbany College of Pharmacy and Health SciencesAlbanyUSA
  2. 2.Department of Pharmaceutical SciencesAlbany College of Pharmacy and Health SciencesAlbanyUSA

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