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

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 35)

Abstract

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.

Keywords

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

Abbreviations

AMPA

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

bb

Basal bodies

BBB

Blood-brain barrier

BRB

Blood-retinal barrier

cc

Connecting cilium

CFH

Complement factor H

cGMP

Cyclic guanosine monophosphate

CIS

Cone inner segment

CNG

Cyclic nucleotide-gated

CNS

Central nervous system

CNTF

Ciliary neurotrophic factor

COS

Cone outer segment

CRABP

Cellular retinaldehyde-binding protein

CRBP

Cellular retinol-binding protein

ER

Endoplasmic reticulum

ERG

Electroretinogram

GABA

γ-Aminobutyric acid

GDP

Guanosine diphosphate

GPCR

G protein-coupled receptor

GTP

Guanosine triphosphate

ILGF-I

Insulin-like growth factor-I

ILM

Inner limiting membrane

IMH

Isomerohydrolase

IPM

Interphotoreceptor matrix

IRBP

Intracellular retinol-binding protein

IS

Inner segment

LEDGF

Lens epithelium-derived growth factor

LGN

Lateral geniculate nucleus

LRAT

Lecithin-retinol acyltransferase

mGlu6

Metabotropic glutamate 6

NPE

Nonpigmented epithelial cells

OLM

Outer limiting membrane

ONL

Outer nuclear layer

OS

Outer segment

PDE

Phosphodiesterase

PDGF

Platelet-derived growth factor

PE

Phosphatidylethanolamine

PE

Pigmented epithelial cells

POS

Photoreceptor outer segment

RBP4

Retinol-binding protein 4

RDH11

Retinol dehydrogenase 11

RDH5

Retinol dehydrogenase 5

RDH8

Retinol dehydrogenase 8

RGC

Retinal ganglion cell

RIS

Rod inner segment

ROS

Rod outer segment

RPE

Retinal pigment epithelium

STRA6

Stimulated by retinoic acid 6 protein

TGF-β

Transforming growth factor-β

TMD

Transmembrane domain

TTR

Transthyretin

Notes

Acknowledgments

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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