Carnitinoid lipoic acid derivatives protect photoreceptors after experimental retinal detachment.

Abstract

Purpose : Retinal detachment (RD) is a vision threatening disease that is characterized by the separation of photoreceptors (PR) from the underlying retinal pigment epithelium (RPE). Since photoreceptors have high demand in energy and metabolism, nutrient deprivation after RD can lead to a compromised function of mitochondria and the generation of reactive oxygen species (ROS) in the photoreceptor layer. However, natural antioxidants have concerns of reduced efficacy due to their limited and transient accumulation following oral intake. Thus, we wanted to investigate the effects of mitoprotectant and antioxidant lipoic acid derivatives in experimental RD.

Methods : Retinal detachment in mice was induced by subretinal administration of hyalauronic acid 1%. The novel synthetic lipoylcarnitine derivative, lipoyl-L-carnitine methyl ester iodide (PMX-500FI) was administered intraperitoneally at 40 mg/kg daily. Cyclodextrin was injected as vehicle control. Animals were euthanized at day 1, 3 and 7 post RD induction. The effects on PR was examined via TUNEL staining and outer nuclear layer (ONL) thickness evaluation. Inflammatory reaction was evaluated via CD11b staining.

Results : PMX-500FI administration led to a significant reduction of TUNEL positive cells in the photoreceptor layer compared to vehicle group (p = 0.009) at 24 hours after RD (Fig. 1). Furthermore, a suppression of infiltrating macrophages in the subretinal space 3 days after RD was noted (p = 0.048) (Fig. 2). Administration of PMX-500FI resulted in a substantial preservation of ONL thickness after 7 days of treatment (p = 0.002).

Conclusions : These results suggest that bioavailable lipoic acid derivative, PMX-500FI, results in protection of photoreceptors after RD and suggest that lipoic acid derivatives may serve as neuroprotectants.

This is a 2020 ARVO Annual Meeting abstract.

 

TUNEL staining after 24 hours RD in vehicle (a, c) and PMX-500FI (b, c) treatment groups. Scale bar: 50µm

 

CD11b staining after 3 days of RD in vehicle (a, c) and PMX-500FI (b, c) treatment groups. Scale bar: 200µm