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

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Drug Delivery Challenges and Novel Therapeutic Approaches for Retinal Diseases

Part of the book series: Topics in Medicinal Chemistry ((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.

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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

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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.

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  1. Department of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

    Christopher L. Cioffi

  2. Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

    Christopher L. Cioffi

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  1. Departments of Basic and Clinical Sciences and Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

    Christopher L. Cioffi

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Cioffi, C.L. (2020). Introduction: Overview of the Human Eye, Mammalian Retina, and the Retinoid Visual Cycle. In: Cioffi, C.L. (eds) Drug Delivery Challenges and Novel Therapeutic Approaches for Retinal Diseases. Topics in Medicinal Chemistry, vol 35. Springer, Cham. https://doi.org/10.1007/7355_2020_94

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