Neuroprotective strategies for retinal disease

Abstract

Diseases that affect the eye, including photoreceptor degeneration, diabetic retinopathy, and glaucoma, affect 11.8 million people in the US, resulting in vision loss and blindness. Loss of sight affects patient quality of life and puts an economic burden both on individuals and the greater healthcare system. Despite the urgent need for treatments, few effective options currently exist in the clinic. Here, we review research on promising neuroprotective strategies that promote neuronal survival with the potential to protect against vision loss and retinal cell death. Due to the large number of neuroprotective strategies, we restricted our review to approaches that we had direct experience with in the laboratory. We focus on drugs that target survival pathways, including bile acids like UDCA and TUDCA, steroid hormones like progesterone, therapies that target retinal dopamine, and neurotrophic factors. In addition, we review rehabilitative methods that increase endogenous repair mechanisms, including exercise and electrical stimulation therapies. For each approach, we provide background on the neuroprotective strategy, including history of use in other diseases; describe potential mechanisms of action; review the body of research performed in the retina thus far, both in animals and in humans; and discuss considerations when translating each treatment to the clinic and to the retina, including which therapies show the most promise for each retinal disease. Despite the high incidence of retinal diseases and the complexity of mechanisms involved, several promising neuroprotective treatments provide hope to prevent blindness. We discuss attractive candidates here with the goal of furthering retinal research in critical areas to rapidly translate neuroprotective strategies into the clinic.

Hexokinase 2 is dispensable for photoreceptor development but is required for survival during aging and outer retinal stress

“…Nearly 10 million individuals in the US alone are affected with either diabetic retinopathy, age-related macular degeneration, or retinitis pigmentosa, and the number of affected adults is only predicted to increase due to the aging population of the United States. 1 Although the pathological mechanisms underlying these various retinal degenerations are complex, the ultimate cause of blindness is the death of photoreceptor cells. Therefore, identifying a common mechanism for promoting photoreceptor cell survival agnostic of the upstream pathological signaling has immense potential for preserving vision in many types of retinal diseases.…”

Protecting the Aging Retina

“…They have been used for liver detoxification, dissolution of gallstone and kidney stone, suppression of convulsions, and visual improvement in traditional Chinese medicine for a very long time. According to the theory of modern medicine, UDCA and TUDCA exhibit neuroprotective effects through prevention of cell apoptosis [69]. TUDCA treatment significantly preserved the number and structure of photoreceptors and retinal functions in different murine models of photoreceptor degeneration, including rd10 mice, rd1 mice, BALB/c mice, Bardet-Biedl syndrome type 1 mice, and transgenic P23H rats [69].…”

Neuroprotection in glaucoma‑electrophysiology (Review)

“…Glaucoma is defined as a group of diseases with progressive loss of the neuroretinal margin of the optic disc that causes characteristic degenerative optic neuropathy (1). There is a sufficient number of studies in the literature focusing on the topic of neuroprotection in glaucoma (2)(3)(4)(5). Therefore, we will not deal with the issue of antioxidants, adenosine receptor antagonists, nicotinic acetylcholine agonists, neurotrophic factors, metabolic products in ganglion cell necrosis and apoptosis, etc.…”