RNA Therapeutics for Retinal Diseases.

Gemayel, Michael C; Bhatwadekar, Ashay D; Ciulla, Thomas

INTRODUCTION In the retina, noncoding RNA (ncRNA) plays an integral role in regulating apoptosis, inflammatory responses, visual perception, and photo-transduction, with altered levels reported in diseased states. AREAS COVERED MicroRNA (miRNA), a class of ncRNA, regulates post-transcription gene expression through the binding of complementary binding sites of target messenger RNA (mRNA) with resulting translational repression. Small interfering RNA (siRNA) are double-stranded RNA (dsRNA) that regulate gene expression, leading to selective silencing of genes through a process called RNA interference (RNAi). Another form of RNAi involves short hairpin RNA (shRNA). In age-related macular degeneration (AMD) and in diabetic retinopathy (DR), miRNA has been implicated in the regulation of angiogenesis, oxidative stress, immune response, and inflammation. EXPERT OPINION Many RNA-based therapies in development are conveniently administered intravitreally, with potential for panretinal effect. The majority of these RNA therapeutics are synthetic ncRNA's and hold promise for the treatment of AMD, DR and inherited retinal diseases (IRDs). These RNA-based therapies include siRNA therapy with its high specificity, shRNA to "knock down" autosomal dominant toxic gain of function mutated genes, antisense oligonucleotides (ASOs), which can restore splicing defects, and translational read-through inducing drugs (TRIDS) to increase expression of full-length protein from genes with premature stop codons.