Prevention and Reversal of Selenite-Induced Cataracts by N-Acetylcysteine Amide in Wistar Rats

Background: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. Methods: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins. Results: Morphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA. Conclusions: The data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss

N-acetyl-L-cysteine Amide Protects Retinal Pigment Epithelium Against Methamphetamine-induced Oxidative Stress

Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which is an em- bryonic extension of the forebrain. The aim of this study, therefore, was to evaluate the pro- tecttive effects of N-acetylcysteine amide (NACA) against oxidative stress induced by METH in retinal pigment epithelium (RPE) cells. Our stud- ies showed that NACA protected against METH- induced oxidative stress in retinal pigment epithelial cells. Although METH significantly de- creased glutathione (GSH) levels and increased reactive oxygen species (ROS) and malondial- dehyde (MDA) levels, these returned to control levels with NACA treatment. Overall observa- tions indicated that NACA protected RPE cells against oxidative cell damage and death by in- hibiting lipid peroxidation, scavenging ROS, in- creasing levels of intracellular GSH, and main- taining the antioxidant enzyme activity and the integrity of the bloodretinal barrier (BRB). The effectiveness of NACA should be further evalu- ated to determine its potential for the treatment of numerous retinal diseases caused by oxidative stress

In Vivo Inhibition of L-buthionine-(S,R)-sulfoximine-induced Cataracts by a Novel Antioxidant, N-acetylcysteine Amide

The effects of N-acetylcysteine amide (NACA), a free radical scavenger, on cataract development were evaluated in Wistar rat pups. Cataract formation was induced in these animals with an intraperitoneal injection of a glutathione (GSH) synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO). to assess whether NACA has a significant impact on BSO-induced cataracts, the rats were divided into four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA + BSO. the control group received only saline ip injections on postpartum day 3, the BSO-only group was given ip injections of BSO (4 mmol/kg body wt), the NACA-only group received ip injections of only NACA (250 mg/kg body wt), and the NACA + BSO group was given a dose of NACA 30 min before administration of the BSO injection. the pups were sacrificed on postpartum day 15, after examination under a slit-lamp microscope. Their lenses were analyzed for selective oxidative stress parameters, including glutathione (reduced and oxidized), protein carbonyls, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. the lenses of pups in both the control and the NACA-only groups were clear, whereas all pups within the BSO-only group developed well-defined cataracts. It was found that supplemental NACA injections during BSO treatment prevented cataract formation in most of the rat pups in the NACA + BSO group. Only 20% of these pups developed cataracts, and the rest retained clear lenses. Further, GSH levels were significantly decreased in the BSO-only treated group, but rats that received NACA injections during BSO treatment had these levels of GSH replenished. Our findings indicate that NACA inhibits cataract formation by limiting protein carbonylation, lipid peroxidation, and redox system components, as well as replenishing antioxidant enzymes

Tofacitinib for refractory uveitis and scleritis

Purpose: To report the successful use of tofacitinib in the treatment of refractory uveitis and scleritis. Observations: Two patients, one with scleritis and another with anterior and intermediate uveitis, presented with refractory disease after failure of multiple steroid-sparing therapies. Treatment with tofacitinib led to durable resolution of uveitis and scleritis. Conclusions and importance: Tofacitinib is a potential novel treatment option for refractory, noninfectious inflammatory eye disease. Keywords: Uveitis, Scleritis, Tofacitinib, JAK, STA

N-acetylcysteine amide (NACA) Prevents Retinal Degeneration Induced by Sodium Iodate in C57BL/6 Mice

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. AMD is a degenerative condition that begins in %UXFK¶V PHPEUDQH and progresses to the retinal pigment epithelium (RPE) and, ultimately, the overlying photoreceptors. Since oxidative stress is strongly implicated in the pathogenesis of AMD, we hypothesized that N-acetylcysteine amide (NACA), a novel thiol antioxidant, would retard progression of retinal degeneration. in order to assess whether NACA had a significant impact on prevention of sodium iodate (NaIO3)-induced (50mg/kg) retinal degeneration, we utilized 2-month-old C57BL/6 mice which were divided into a control group, a NACA-only group, a NaIO3-induced retinal degeneration group, and a NACA-treated retinal degeneration group. We measured the degrees of photoreceptor cell death and function in the mice using both an electroretinogram (ERG) and analysis of photoreceptor histology, the thickness of the outer nuclear layer (ONL). Our results indicated that treatment with NACA eye drops significantly prevented the reduction in mean peak amplitude of scotopic and photopic waves and reduction in ONL thickness induced by sodium iodate. NACA demonstrated preservation of visual potential and the photoreceptor function in the NaIO3-induced retinal degeneration. in addition, NACA was able to increase the retinal glutathione (GSH) levels in NaIO3treated mice. These results illustrated that NACA can prevent photoreceptor degeneration and loss of visual potential in vivo and, therefore, this nontoxic and potent antioxidant should be considered for the treatment of AMD