Romano Giovanni Luca, Gozzo Lucia, Maurel Oriana Maria, Di Martino Serena, Riolo Valentina, Micale Vincenzo, Drago Filippo, Bucolo Claudio
Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95100 Catania, Italy.
Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95100 Catania, Italy.
Pharmaceutics. 2023 Apr 29;15(5):1370. doi: 10.3390/pharmaceutics15051370.
To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage.
Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR.
PERG amplitude values were significantly ( < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly ( < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly ( < 0.05) after I/R injury. FLX treatment was able to significantly ( < 0.05) attenuate the expression of inflammatory markers after I/R damage.
Topical treatment with FLX was effective in counteracting the damage of RGCs and preserving retinal function. Moreover, FLX treatment attenuates the production of pro-inflammatory molecules elicited by retinal I/R damage. Further studies need to be performed to support the use of FLX as neuroprotective agent in retinal degenerative diseases.
评估局部眼部应用氟西汀(FLX)对急性视网膜损伤小鼠模型的神经保护作用。
利用C57BL/6J小鼠的眼部缺血/再灌注(I/R)损伤诱导视网膜损伤。将小鼠分为三组:对照组、I/R组和局部应用FLX治疗的I/R组。使用图形视网膜电图(PERG)作为视网膜神经节细胞(RGC)功能的敏感测量指标。最后,通过数字液滴PCR分析视网膜炎症标志物(IL-6、TNF-α、Iba-1、IL-1β和S100β)的mRNA表达。
与I/R组相比,I/R-FLX组的PERG振幅值显著更高(<0.05),而与I/R组相比,I/R-FLX治疗的小鼠PERG潜伏期值显著降低(<0.05)。I/R损伤后视网膜炎症标志物显著增加(<0.05)。FLX治疗能够显著(<0.05)减轻I/R损伤后炎症标志物的表达。
局部应用FLX可有效对抗RGC损伤并保留视网膜功能。此外,FLX治疗可减轻视网膜I/R损伤引发的促炎分子的产生。需要进一步开展研究以支持将FLX用作视网膜退行性疾病的神经保护剂。