SPG302 mitigates diabetic retinal neuropathy and inner retinal damage in a genetic mouse model of diabetes

Area of Science:

• Ophthalmology
• Neuroscience
• Endocrinology

Background:

• Diabetic retinopathy (DR) causes vision loss through vascular and neurodegenerative issues.
• Diabetic retinal neuropathy (DRN), an early DR feature, involves inner retinal degeneration and ganglion cell (GC) loss.
• Glutamatergic synapse loss in DR precedes neuron loss, presenting a therapeutic target.

Purpose of the Study:

• To evaluate the therapeutic potential of SPG302 for protecting the inner retina in diabetic retinopathy.
• To assess SPG302's effects on GC function, cell number, synaptic markers, and cell death in a diabetic mouse model.

Main Methods:

• Db/db mice, a diabetic model, were treated with SPG302 or vehicle for 8 weeks.
• Electroretinography (ERG) assessed GC function; retinal tissues were analyzed for GCs, synaptic markers, glial markers, and cell death markers.
• Db/+ mice served as controls.

Main Results:

• Diabetic db/db mice showed significant GC dysfunction, cell loss, synapse loss (decreased PSD95, synaptophysin), increased gliosis, and cell death markers (pBAD, BAX).
• SPG302 treatment significantly preserved retinal integrity by reversing these pathological changes.
• SPG302 did not alter metabolic parameters like weight, hyperglycemia, or glucose/insulin intolerance in db/db mice.

Conclusions:

• SPG302 demonstrates significant neuroprotective effects on the inner retina in a mouse model of diabetes.
• SPG302 effectively mitigates diabetic retinal neuropathy (DRN) by preserving retinal structure and function.
• SPG302 holds therapeutic potential for treating diabetic retinopathy and preventing vision loss associated with DRN.