Tauroursodeoxycholic Acid (TUDCA) Protects Photoreceptors From Cell Death During Experimental Retinal Detachment

Abstract

Purpose: : Surgery for retinal detachment in humans is often successful at anatomical reattachment of the retina, yet the resulting visual acuity can sometimes remain poor. This study tests whether the systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment. TUDCA has its origins in ancient Eastern medicine and recently has been demonstrated to show a number of cytoprotective effects in a variety of experimental systems.

Methods: : An experimental retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with an intraperitoneal injection of vehicle or TUDCA (500 mg/ kg). Preservation of photoreceptors was evaluated by measuring the relative thickness of the outer nuclear layer in histological sections. TUNEL staining was also used to directly evaluate cell death. Macrophages were stained with CD68 using immunohistochemistry, and cytokine levels were measured by ELISA. Oxidative stress was evaluated using an ELISA for carbonyl-protein adducts.

Results: : After three days of detachment, the normalized thickness of the outer nuclear layer decreased to 0.65±0.03, while the ratio of the TUDCA-treated group remained higher at 0.84±0.03. (P=0.002). TUDCA-treated retinas contained decreased TUNEL-positive cells (651±68) comparing to vehicle (1314±68, P=0.001) after 3 days. Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and levels of selected cytokines were not affected by TUDCA treatment. However, an increase in carbonyl-protein adducts as a result of oxidative stress after retinal detachment was almost completely abolished by TUDCA treatment.

Conclusions: : This study demonstrates that systemic administration of the bile acid TUDCA can preserve photoreceptors during retinal detachment. This effect was not mediated by changes in macrophage recruitment or cytokine levels but rather through inhibition of increases in oxidative stress. Observation of this neuroprotective effect of TUDCA in rodents strengthens the hypothesis that administration of TUDCA before and/or after retinal reattachment surgery in humans could preserve visual function.

Keywords: retinal detachment • neuroprotection • cell survival