Therapeutic targets for altering mitochondrial dysfunction associated with diabetic retinopathy

ABSTRACT

Introduction: Retinopathy remains as one of the most feared blinding complications of diabetes, and with the prevalence of this life-long disease escalating at an alarming rate, the incidence of retinopathy is also climbing. Although the cutting edge research has identified many molecular mechanisms associated with its development, the exact mechanism how diabetes damages the retina remains obscure, limiting therapeutic options for this devastating disease.

Areas covered: This review focuses on the central role of mitochondrial dysfunction/damage in the pathogenesis of diabetic retinopathy, and how damaged mitochondria initiates a self-perpetuating vicious cycles of free radicals. We have also reviewed how mitochondria could serve as a therapeutic target, and the challenges associated with the complex double mitochondrial membranes and a well-defined blood-retinal barrier for optimal pharmacologic/molecular approach to improve mitochondrial function.

Expert opinion: Mitochondrial dysfunction provides many therapeutic targets for ameliorating the development of diabetic retinopathy including their biogenesis, DNA damage and epigenetic modifications. New technology to enhance pharmaceuticals uptake inside the mitochondria, nanotechnology to deliver drugs to the retina, and maintenance of mitochondrial homeostasis via lifestyle changes and novel therapeutics to prevent epigenetic modifications, could serve as some of the welcoming avenues for a diabetic patient to target this sight-threatening disease.

KEYWORDS:

• Diabetes
• diabetic retinopathy
• epigenetics
• mitochondria
• mitochondrial DNA
• reactive oxygen species
• retina

Article highlights

Mitochondria, the powerhouse of a cell, play central role in the pathogenesis of diabetic retinopathy, a blinding disease which affects over 85% of patients after 15-20 years of diabetes.Understanding the mechansism(s) of mitochondrial damage is important in idnetifying therapeutical targets to mantain their homeostasis, and help diabetic patients from this devastating disease.

Acknowledgments

The authors thank their laboratory associates, especially Dr. Arul J. Duraisamy, for some of the initial literature research.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article is supported in part by the grants to RAK from the National Institutes of Health [EY014370, EY017313 and EY022230], Juvenile Diabetes Research Foundation [1-2008-764 and 5-2012-13] and the Thomas Foundation, and an unrestricted grant to the Ophthalmology Department from Research to Prevent Blindness.