Iron role in retinal detachment and neuroprotective effects of transferrin

Abstract

Purpose : Retinal detachment (RD), characterized by the separation of the neuroretina from the retinal pigment epithelium (RPE), often leads to permanent visual impairment. Iron is known to be implicated in degenerative diseases and its excess enhances neural cells death. In models of retinal degeneration, we have previously demonstrated iron accumulation in the outer retina, and the neuroprotective effect of a natural iron chelator, transferrin (TF), after local administration. Here, we have investigated the involvement of iron in RD and the possible neuroprotective effect of TF treatment.

Methods : Iron status was assessed in ocular fluids from patients with RD and compared to controls. Iron was also detected on RD human retinal sections by Perl’s reaction and Inductively Coupled Plasma Mass Spectrometry. An organoculture system of murin retinas was created, on which the dose-dependent effects of iron were evaluated, and the protective effects of TF were screened. Rodent models of RD were produced by subretinal injection of sodium hyaluronate. Mice expressing human TF were used to evaluate survival of photoreceptors in detached neural retina.

Results : Elevated iron levels and fully saturated TF were found in the vitreous of RD patients compared to control ones. Iron was also detected in sub-retinal fluids (SRF). Iron level in SRF was significantly correlated to duration of RD, and associated with a worse post-operative visual recovery. Moreover, iron deposits were detected in the neuroretina and RPE. In organocultured mice retinas, addition of iron in culture media leads to its accumulation in the retina, cones death and decreases of rhodopsin protein level. After experimental RD in mice, intraretinal iron deposits and photoreceptors loss were observed. Expression of TF in RD mice model preserved against retinal edema, photoreceptor outer segments shortening and cone loss. Moreover, inflammation was decreased, iron metabolism was controlled and oxidative stress reduced.

Conclusions : Our results showed iron accumulation in the retina and ocular fluids during RD and the involvement of iron in the pathophysiology of retinal cell damage following RD. Moreover, we demonstrated the potential of TF as adjuvant therapeutic agent, preventing vision loss in RD and associated diseases.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.