Resveratrol as a Corneal Pain Therapeutic

More thanindividuals undergo laser vision correction surgery each year in the United Statesincluding laser assisted in situ keratomileusisLASIKand photorefractive keratectomyPRKThese procedures damage the nerves in the corneal epithelium causing intense acute pain that most patients rate as greater thanon ascalemany report the pain to beunbearableeven after analgesic treatmentWhile virtually all patients will experience acute painup towill also experience chronic dry eye after corrective surgeryThis is likely because damage to corneal sensory nerves disrupts afferent signaling that causes tear production in response to the sensation of dryness at the ocular surfaceThe patients who develop chronic dry eye disease are also at risk for developing chronic painCurrent approaches to managing pain after PRK include systemic and topical nonsteroidal anti inflammatory drugs and opioidsbut these medications have potentially severe side effects including gastric distress with NSAIDs and addiction with opioidsThusbetter analgesics for ocular surgical procedures represents a large unmet clinical needResveratrol is a natural polyphenol found in red grapes and other plant sources and has been shown in preclinical models to attenuate both acute and chronic incision pain as well as prevent the transition to a chronic pain stateResveratrol is thought to reduce pain by activating AMP activated protein kinaseAMPKand engaging its downstream mechanismsIt possesses appropriate chemical properties for topical dosing and tissue permeationi eit is highly lipophilicis already viewed as safe for human consumption by the FDAand is approved as an active antioxidant ingredient for topical formulasnon cornealThe Aicher laboratory has developed a preclinical model of PRK that uses heptanol to remove the corneal epithelium and produce an abrasion that shears terminal nerve endings in the epitheliumThis preclinical model mimics the epithelial neuronal damage produced by PRK in humans and causes key post operative symptomsincluding acute pain and chronic dry eyemaking it an ideal model to test novel therapeutics to attenuate PRK painOur proposed studies will test the hypothesis that resveratrol containing eye drops can be used as a novel therapeutic for corneal pain using this preclinical model of PRKWe will first test whether resveratrol has efficacy for corneal hyperalgesiaAimand dry eye symptomsAimafter abrasion injury in the ratThese studies will then assess whether resveratrol interferes will epithelial repair after injuryAimTogether these experiments will generate preclinical rationale for the development of resveratrol for the treatment of PRK painand potentially for use in other ocular surgical procedures More thanindividuals undergo laser vision correction surgery each year in the United Stateswhich damages the nerves in the corneal epithelium causing intense acute pain and chronic dry eyeCurrent approaches to managing pain after vision correction surgery include systemic and topical nonsteroidal anti inflammatory drugs and opioidsbut these medications do not have adequate efficacy and they also have the potential for addiction with opioidsOur proposed studies will use a preclinical model of photorefractive keratectomyPRKthat mimics the epithelial neuronal damage produced by PRK in humans and causes key post operative symptoms including pain and dry eyeto test the hypothesis that resveratrol containing eye drops can be used as a novel therapeutic for corneal pain