Treatment of Laser-Induced Retinal Injury and Visual Loss Using Sustained Release of Intra-Vitreal Neurotrophic Growth Factors

Abstract

Purpose: : To develop a novel therapeutic approach to laser retinal damage using intravitreal injection of microspheres with sustained release of glial cell-derived neurotrophic factor (GDNF).

Methods: : Laboratory beagles (n=20) with experimentally induced laser retinal damage were divided into 3 groups: group 1 received intravitreal injection of GDNF-PLGA spheres (with degradation and release kinetics of 3 months) 1 hour after damage induction (GDNF1), group 2 received empty spheres (E2) and group 3 received laser damage but no additional treatment (LT3). Functional (pattern and ISCEV ERG) recordings were done at 14, 30, 90 and 180 days post laser exposure.

Results: : Ninety days after laser exposure, significant decrease in scotopic a-wave amplitude was present in dogs which received empty microspheres (mean ± SEM: 86.51 ± 3.97µV, p=0.0044, unpaired t-test) and dogs which received laser damage only (56.95 ± 3.77µV, p<0.0001), but not in GDNF treated dogs (113.8 ± 11.03µV, p=0.5041) when compared to healthy controls (123.3 ± 8.49µV). However, 180d post laser injury, a-wave amplitude significantly decreased in GDNF-treated group (48.4 ± 7.27µV, p<0.0001) when compared to control values and was not significantly different when compared to values in dogs, which received empty spheres (45.63±4.39µV, p=0.9455) or dogs with laser damage only (42.75±5.58µV, p=0.671).Almost identical trend of changes has been observed with inner retina function (b-wave amplitudes and oscillatory potentials).

Conclusions: : Intravitreal injection of microspheres with sustained release of GDNF protected retinal function in laser-damaged eyes for 3 months. At six months post laser injury, when GDNF was no longer present in the eyes, functional deficits continued to progress, which is suggestive of progressive loss of retinal function even months after initial laser damage in an environment depleted of neurotrophic support.

Keywords: laser • retina: distal (photoreceptors, horizontal cells, bipolar cells) • neuroprotection