Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation. TGFβ signaling regulates LEC proliferation and differentiation as well, but also promotes epithelial-mesenchymal transitions that lead to cataracts. Thus far, it has been difficult to recapitulate the features of germinative LECs in vitro. Here, we have established a LEC culture protocol that uses SB431542 (SB) compound to inhibit TGFβ/Smad activation, and found that SB treatment promoted mouse LEC proliferation, maintained LECs’ morphology and distinct markers including N-cadherin, c-Maf, Prox1, and αA-, αB-, and β-crystallins. In contrast, low-dosage bFGF was unable to sustain those markers and, combined with SB, altered LECs’ morphology and β-crystallin expression. We further found that Matrigel substrate coatings greatly increased cell proliferation and uniquely affected β-crystallin expression. Cultured LECs retained the ability to differentiate into γ-crystallin-positive lentoids by high-dosage bFGF treatment. Thus, a suppression of TGFβ/Smad signaling in vitro is critical to maintaining characteristic features of mouse LECs, especially expression of the key transcription factors c-Maf and Prox1.
Importance This is the first study to compare the efficacy and safety of endocyclophotocoagulation (ECP) via pars plana (ECP‐plus) with ECP via limbus (anterior ECP) for treating glaucoma. Background There is no direct comparison of treatment outcomes between ECP‐plus and anterior ECP. Design Retrospective study. Participants Fifty‐four consecutive patients. Methods Fifty‐eight eyes from 54 consecutive patients underwent anterior ECP (33 eyes) or ECP‐plus (25 eyes) with 2‐year follow‐up. Linear mixed model was used to analyse the surgical outcomes. Main Outcome Measures Intraocular Pressure (IOP) was the primary outcome. Secondary outcomes were best‐corrected visual acuity, number of glaucoma medications, complications and success rate. Results Compared to anterior ECP, patients in the ECP‐plus group had lower IOP (estimate of effect size [EES] = −3.7 mmHg, P = 0.023) and used fewer number of glaucoma medications (EES = −1.11, P = 0.003), after adjusting for degrees of treatment, preoperative IOP, and presence of combined ECP and phacoemulsification procedure. Patients with ECP‐plus achieved a higher success rate at 2 years postoperatively (80% vs 33.3%, P < 0.001). The decrease in IOP between the preoperative and last follow‐up visit was greater in the ECP‐plus group compared to the anterior ECP group (14.3 mmHg (52%) vs 5.2 mmHg (24%), P = 0.001). There was no significant difference in complication rates between the two groups (28% vs 33%, P = 0.561). Conclusions and Relevance Anterior ECP and ECP‐plus have a similar safety profile, and ECP‐plus may offer superior IOP control for the management of glaucoma.
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