Aldose reductase, ocular diabetic complications and the development of topical Kinostat®

Peter F Kador, Milton Wyman, Peter J. Oates

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is a major health problem with devastating effects on ocular health in both industrialized and developing countries. The control of hyperglycemia is critical to minimizing the impact of DM on ocular tissues because inadequate glycemic control leads to ocular tissue changes that range from a temporary blurring of vision to permanent vision loss. The biochemical mechanisms that promote the development of diabetic complications have been extensively studied. As a result, a number of prominent biochemical pathways have been identified. Among these, the two-step sorbitol pathway has been the most extensively investigated; nevertheless, it remains controversial. To date, long-term pharmacological studies in animal models of diabetes have demonstrated that the onset and development of ocular complications that include keratopathy, retinopathy and cataract can be ameliorated by the control of excess metabolic flux through aldose reductase (AR). Clinically the alleles of AR have been linked to the rapidity of onset and severity of diabetic ocular complications in diabetic patient populations around the globe. In spite of these promising preclinical and human genetic rationales, several clinical trials of varying durations with structurally diverse aldose reductase inhibitors (ARIs) have shown limited success or failure in preventing or arresting diabetic retinopathy. Despite these clinical setbacks, topical ARI Kinostat® promises to find a home in clinical veterinary ophthalmology where its anticipated approval by the FDA will present an alternative treatment paradigm to cataract surgery in diabetic dogs. Here, we critically review the role of AR in diabetes mellitus-linked ocular disease and highlight the development of Kinostat® for cataract prevention in diabetic dogs. In addition to the veterinary market, we speculate that with further safety and efficacy studies in humans, Kinostat® or a closely related product could have a future role in treating diabetic keratopathy.

Original languageEnglish (US)
Pages (from-to)1-29
Number of pages29
JournalProgress in Retinal and Eye Research
Volume54
DOIs
StatePublished - Sep 1 2016

Fingerprint

Aldehyde Reductase
Diabetes Complications
Cataract
Diabetes Mellitus
Dogs
Sorbitol
Eye Diseases
Health
Medical Genetics
Diabetic Retinopathy
Ophthalmology
Developed Countries
Hyperglycemia
Developing Countries
Animal Models
Alleles
Clinical Trials
Pharmacology
Safety
Population

Keywords

  • Aldose reductase inhibitor
  • Diabetic cataract
  • Diabetic keratopathy
  • Diabetic retinopathy
  • Kinostat

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Aldose reductase, ocular diabetic complications and the development of topical Kinostat®. / Kador, Peter F; Wyman, Milton; Oates, Peter J.

In: Progress in Retinal and Eye Research, Vol. 54, 01.09.2016, p. 1-29.

Research output: Contribution to journalReview article

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