Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model

• Published in: Current eye research Vol. 48; no. 7; pp. 618 - 626
• Main Authors: He, Na, Zhang, Xiangxiang, Xie, Peiling, He, Jialing, Lv, Zhigang
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.07.2023
• Subjects: Adenoviridae - genetics; Animals; Capsule Opacification - genetics; Capsule Opacification - metabolism; Capsule Opacification - prevention & control; Cataract - metabolism; Cataract surgery; Epithelial Cells - metabolism; gene therapy; Inflammation - metabolism; lens epithelial cells; posterior capsule opacification; Rabbits; RNA, Small Interfering - genetics; Telomerase - genetics; Telomerase - metabolism; TERT; Cataract surgery; gene therapy; TERT; posterior capsule opacification; lens epithelial cells
• ISSN: 0271-3683; 1460-2202
• DOI: 10.1080/02713683.2023.2194587

Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery and cannot yet be eliminated. Here, we investigated the inhibitory effects of telomerase reverse transcriptase (TERT) gene silencing on PCO in a rabbit model. After rabbit lens epithelial cells (LECs) were treated with adenovirus containing short hairpin RNAs (shRNA) targeting TERT (shTERT group), adenovirus containing scramble nonsense control shRNA (shNC group) or PBS (control group), quantitative real-time polymerase chain reaction and Western blotting were used to measure the expression levels of TERT, and a scratch assay was performed to assess the LEC migration. New Zealand white rabbits underwent sham cataract surgery followed by an injection of adenovirus carrying shTERT into their capsule bag. The intraocular pressure and anterior segment inflammation were evaluated on certain days, and EMT markers (α-SMA and E-cadherin) were evaluated by Western blotting and immunofluorescence. The telomerase activity of the capsule bag was detected by ELISA. At 28 d postoperatively, hematoxylin and eosin staining of the cornea and iris and electron microscopy of the posterior capsule were performed. Application of shTERT to LECs downregulated the expression levels of TERT mRNA and protein. The scratch assay results showed a decrease in the migration of LECs in the shTERT group. In vivo, shTERT decreased PCO formation after cataract surgery in rabbits and downregulated the expression of EMT markers, as determined by Western blotting and immunofluorescence. In addition, telomerase activity was suppressed in the capsule bag. Despite slight inflammation in the iris, histologic results revealed no toxic effects in the cornea and iris. TERT silencing effectively reduces the migration and proliferation of LECs and the formation of PCO. Our findings suggest that TERT silencing may be a potential preventive strategy for PCO.