Abstract
Purpose :
Neurodegeneration has a central role in the pathogenesis of diabetic retinopathy (DR). Therefore, many studies proposed neuroprotection as an effective therapeutic strategy for DR. Forskolin (FSK) is a natural product that has already shown efficacy in IOP reduction following topical application. In an Alzheimer disease model, it was found to provide neuroprotection via attenuation of microglial activation. In this study, using a well-established model of DR, we aim to assess FSK potential neuroprotection and modulation of retinal glial cells plasticity.
Methods :
Diabetes mellitus (DM) was induced in young adult albino rats by intraperitoneal injection (IP) of 100 mg/kg Streptozotocin (STZ) (n=6). 8 weeks after DM induction, right eyes received intravitreal injection of FSK (6 nmol/eye), while the contralateral left eyes served as control. Rats with fasting blood glucose level ≤ 200 mg/dL after STZ injection, lens injuries or vitreous hemorrhage after intravitreal injection were excluded. Control rats (n=6) received IP of 0.5mL of saline. 1 week after FSK injection, all eyes were immunofluorescent stained with NEUN, Caspase 3, IBA1 and GFAP to label Neuron, apoptosis, microglia and astrocyte respectively.
Results :
DR caused ganglion cell apoptosis with significant decrease of neuron cell number when compared to control group (p <0.0001). DR induced neuron death was associated with microglia activation and reactive astrocyte gliosis. Interestingly, intravitreal FSK treatment significantly improved the neuronal survival in DR (p=0.01). Unexpectedly, this neuroprotective effect of FSK occurred without altering the DR induced astrocyte/microglia activation.
Conclusions :
FSK ameliorates neuron cell death in a rat model of DR. Given its previously tested ocular safety, FSK could be a potential therapeutic target for DR.
This is a 2020 ARVO Annual Meeting abstract.