Maddirala Yasaswi, Tobwala Shakila, Karacal Humeyra, Ercal Nuran
Department of Chemistry, Missouri University of Science and Technology, Rolla, MO, 65409, USA.
Department of Ophthalmology, Washington University, St. Louis, MO, 63110, USA.
BMC Ophthalmol. 2017 Apr 26;17(1):54. doi: 10.1186/s12886-017-0443-1.
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.
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.
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.
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.
本研究旨在评估N - 乙酰半胱氨酸酰胺(NACA)滴眼液对逆转雄性Wistar大鼠幼崽中由亚硒酸钠诱导的白内障形成的疗效。
40只雄性Wistar大鼠幼崽被随机分为对照组、仅使用N - 乙酰半胱氨酸酰胺组、亚硒酸钠诱导的白内障组和NACA治疗的亚硒酸钠诱导的白内障组。在产后第10天腹腔注射亚硒酸钠,而在相应组中,于产后第9、11和13天腹腔注射N - 乙酰半胱氨酸酰胺。在大鼠幼崽睁眼的第2周结束时(产后第14天)评估白内障情况。从第3周开始直至第4周结束(产后第15至30天)给予N - 乙酰半胱氨酸酰胺滴眼液,并在第4周结束时处死大鼠。分离晶状体并检测氧化应激参数,如谷胱甘肽、脂质过氧化和钙水平,以及谷胱甘肽还原酶和硫醇转移酶的活性。使用晶状体蛋白的水溶性部分进行酪蛋白酶谱分析和m - 钙蛋白酶的蛋白质印迹分析。
NACA治疗组晶状体的形态学检查表明,NACA能够逆转白内障分级。此外,NACA治疗组的谷胱甘肽水平、硫醇转移酶活性、m - 钙蛋白酶活性和m - 钙蛋白酶水平(通过蛋白质印迹评估)均显著高于亚硒酸钠诱导的白内障组。此外,注射亚硒酸钠的大鼠幼崽的丙二醛、谷胱甘肽还原酶活性和钙水平显著更高,在用NACA治疗后降至对照水平。
数据表明,NACA有潜力显著改善视力并减轻与白内障相关的功能丧失负担。白内障形成的预防和逆转可能具有全球影响。开发像NACA这样的药物最终可能预防高危人群中的白内障形成,并可能预防早期白内障的进展。这带来了从昂贵的白内障手术治疗到相对便宜的预防视力丧失的范式转变。