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  • Review Article
  • Published:

Ophthalmic drug discovery

Nature Reviews Drug Discovery volume 2, pages 448–459 (2003)Cite this article

Key Points

  • The success of a number of drugs to treat ocular diseases has resulted in an increased interest in ocular drug discovery.

  • The eye represents a unique and challenging complex organ for applying therapeutics, particularly with respect to drug delivery and access to selective ocular sites.

  • Disease entities covered in the review include diabetes retinopathy, age-related macular degeneration, glaucoma, dry eye, cataract, ocular inflammation and ocular infections.

  • Emphasis is placed on pathophysiology and the identity of target sites for retinal diseases and glaucoma, with present and potential drug therapies and screening models highlighted.

  • Target mechanisms discussed included angiogenesis, apoptosis and the extracellular matrix.

  • Sites for potential therapeutic intervention are identified.

Abstract

Millions of people suffer from a wide variety of ocular diseases, many of which lead to irreversible blindness. The leading causes of irreversible blindness in the elderly — age-related macular degeneration and glaucoma — will continue to effect more individuals as the worldwide population continues to age. Although there are therapies for treating glaucoma, as well as ongoing clinical trials of treatments for age-related macular degeneration, there still is a great need for more efficacious treatments that halt or even reverse ocular diseases. The eye has special attributes that allow local drug delivery and non-invasive clinical assessment of disease, but it is also a highly complex and unique organ, which makes understanding disease pathogenesis and ocular drug discovery challenging. As we learn more about the cellular mechanisms involved in age-related macular degeneration and glaucoma, potentially, new drug targets will emerge. This review provides insight into some of the new approaches to therapy.

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Figure 1: Ocular tissues and common ocular diseases.
Figure 2: Drug targets for neuroprotection.
Figure 3: Mechanism of action for ocular angiostatic agents in clinical development.

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Authors and Affiliations

  1. Alcon Research, Ltd, Fort Worth, 76134, Texas, USA

    Abbot F. Clark & Thomas Yorio

  2. Department of Pharmacology and Neuroscience, Graduate School of Biomedical Science, University of North Texas Health Science Center, Fort Worth, 76107-2699, Texas, USA

    Abbot F. Clark

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Correspondence to Abbot F. Clark.

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DATABASES

LocusLink

CYP1B1

endothelin-1

FOXC1

MYOC

OPTN

PITX2

RPE65

FURTHER INFORMATION

RetNet

Glossary

CATARACT

An opacity of the lens that causes the loss of transparency and/or the scattering of light entering the eye.

AGE-RELATED MACULAR DEGENERATION

Retinal neurodegenerative disease of the aged that leads to the progressive loss of central vision.

GLAUCOMA

A heterogeneous group of optic neuropathies that lead to progressive vision loss and blindness.

OPHTHALMOLOGY

The branch of medicine that deals with the eye and eye diseases.

TRABECULAR MESHWORK

Reticulated tissue at the junction of the iris and cornea which imparts resistance to aqueous humour outflow and thereby regulates intraocular pressure.

OPTIC NERVE HEAD

Region at the back of the eye where ∼1 million retinal ganglion cell axons exit the eye through the sclera to form the optic nerve.

OCULAR HYPERTENSION

Condition in which the pressure inside the eye (intraocular pressure) is higher than normal (usually defined as >21 mm Hg)

MATRIX METALLOPROTEINASES

Family of extracellular enzymes responsible for the degradation and turnover of extracellular matrix molecules.

RETINOPATHY

Degenerative disease of the retina, which is the multilayered neural tissue of the eye responsible for phototransduction and integration of visual signals.

VASCULAR ENDOTHELIAL GROWTH FACTOR

A cytokine responsible for vascular leakage and neovascularization.

DRUSEN

Deposits containing complex lipids and calcium that can accumulate with age.

BRUCH'S MEMBRANE

Basement membrane that separates the retinal pigment epithelium from the vascular choroid.

MACULA

Central region of the retina with the highest concentration of cone photoreceptors that is responsible for color and acute vision.

DRY EYE

A condition characterized by ocular discomfort and caused be ocular tissue deficiencies.

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Clark, A., Yorio, T. Ophthalmic drug discovery. Nat Rev Drug Discov 2, 448–459 (2003). https://doi.org/10.1038/nrd1106

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