Kamuvudine-9 Protects Retinal Structure and Function in a Novel Model of Experimental Rhegmatogenous Retinal Detachment.

Purpose: Rhegmatogenous retinal detachment (RRD) is a vision-threatening event that benefits from surgical intervention. While awaiting surgical reattachment, irreversible hypoxic and inflammatory damage to the retina often occurs. An interim therapy protecting photoreceptors could improve functional outcomes. We sought to determine whether Kamuvudine-9 (K-9), a derivative of nucleoside reverse transcriptase inhibitors (NRTIs) that inhibits inflammasome activation, and the NRTIs lamivudine (3TC) and azidothymidine (AZT) could protect the retina following RRD. Methods: RRD was induced in mice via subretinal injection (SRI) of 1% carboxymethylcellulose (CMC). To simulate outcomes following the clinical management of RRD, we determined the optimal conditions by which SRI of CMC induced spontaneous retinal reattachment (SRR) occurs over 10 days (RRD/SRR). K-9, 3TC, or AZT was administered via intraperitoneal injection. Inflammasome activation pathways were monitored by abundance of cleaved caspase-1, IL-18, and cleaved caspase-8, and photoreceptor death was assessed by TUNEL staining. Retinal function was assessed by full-field scotopic electroretinography. Results: RRD induced retinal inflammasome activation and photoreceptor death in mice. Systemic administration of K-9, 3TC, or AZT inhibited retinal inflammasome activation and photoreceptor death. In the RRD/SRR model, K-9 protected retinal electrical function during the time of RRD and induced an improvement following retinal reattachment. Conclusions: K-9 and NRTIs exhibit anti-inflammatory and neuroprotective activities in experimental RRD. Given its capacity to protect photoreceptor function during the period of RRD and enhance retinal function following reattachment, K-9 shows promise as a retinal neuroprotectant and warrants study in RRD. Further, this novel RRD/SRR model may facilitate experimental evaluation of functional outcomes relevant to RRD.

Reduction of human Alzheimer's disease risk and reversal of mouse model cognitive deficit with nucleoside analog use.

Innate immune signaling through the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer's disease (AD), the most prevalent form of dementia. We previously demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs), drugs approved to treat HIV and hepatitis B infections, also inhibit inflammasome activation. Here we report that in humans, NRTI exposure was associated with a significantly lower incidence of AD in two of the largest health insurance databases in the United States. Treatment of aged 5xFAD mice (a mouse model of amyloid-ß deposition that expresses five mutations found in familial AD) with Kamuvudine-9 (K-9), an NRTI-derivative with enhanced safety profile, reduced Aß deposition and reversed their cognitive deficit by improving their spatial memory and learning performance to that of young wild-type mice. These findings support the concept that inflammasome inhibition could benefit AD and provide a rationale for prospective clinical testing of NRTIs or K-9 in AD.

Zero Phaco: A new technique for dealing with soft cataracts.

Phacoemulsification in soft cataracts can be challenging due to the lack of rigid cleavage planes and the inability to crack. We describe a new phacoemulsification technique for dealing with soft cataracts using high vacuum and zero energy. Following capsulorhexis and hydrodissection, we introduced the phacoemulsification probe, keeping the torsional and longitudinal power at zero. A central groove was created in sculpting mode. We held the nucleus with adequate vacuum in chop mode and divided the nucleus. Then, we rotated and chopped the nucleus similarly into small pieces without using any power. For emulsification, we increased the vacuum to 600 mmHg and then shredded and stuffed the pieces into the phaco probe by the chopper. A newer generation phaco machine with active fluidic system and monitored pressurized infusion helps the surgeon control the intraocular pressure (IOP) and hold the nucleus with vacuum alone, allowing chopping and emulsifying of the pieces without any energy.

Comparison of once daily dose of 0.3% nepafenac alone and three times dose of 0.1% nepafenac alone in pain and inflammation control after phacoemulsification.

PURPOSE: To compare the efficacy of a once-daily dose of 0.3% nepafenac and three times daily dose of 0.1% nepafenac in controlling pain and inflammation following phacoemulsification. METHODS: In this prospective randomized control single-blind study. patients who underwent uneventful phacoemulsification were divided into two groups. Group A received 0.1% nepafenac eye drops three times/day for 4 weeks and group B received 0.3% nepafenac eye drops once daily for 4 weeks following phacoemulsification. All the patients received moxifloxacin 0.5% eye drops four times/day for 2 weeks. None of the patients in any group received any form of corticosteroids. RESULTS: The mean age of the patients in group A was 63.55 ± 8.5 years, while in group B, it was 60.05 ± 7.76 years. There was no significant result in the preoperative baseline demographics and intraoperative parameters between both the groups. The results were statistically insignificant in terms of inflammatory markers between both groups on day 1. But, on day 7, group B showed better results in terms of lid edema, conjunctival congestion, and anterior chamber cells. The patients in group B also perceived significantly less pain on day 1 (P = 0.02) and day 7 (P < 0.001). The central macular thickness was also significantly lower in group B at day 30. (: P < .001) and day 90 (P < .001), respectively. CONCLUSION: Once-daily dose of higher concentrated nepafenac (0.3%) is equally effective and shows better results than 0.1% nepafenac for pain and inflammation control.