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1.
Exp Eye Res ; 204: 108447, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33465394

RESUMO

We previously found that epigallocatechin-3-gallate (EGCG) could inhibit the myofibroblast transformation of human Tenon's fibroblasts, however, the underlying mechanism remained unclear. We therefore investigated whether the autophagic regulation involved in the anti-fibrotic function of EGCG. The fibroblasts were subjected to transforming growth factor beta-1 (TGF-ß1) induction followed by EGCG treatments. The autophagic flux was examined by transmission electron microscopy and autophagic flux analysis. The levels of autophagy-related proteins (LC3ß and p62) and alpha-smooth muscle actin (α-SMA) were measured by Western blot and immunofluorescence. Results showed that TGF-ß1 partially inhibited the autophagic function of Tenon's fibroblasts. But this inhibition effect was rescued by LY2157299, a TGF-ßR1 selective inhibitor. Compared with the cells treated with TGF-ß1 alone, EGCG treatments increased the amount of autophagosomes and autolysosomes, evaluated the ratio of LC3-II to LC3-I and decreased p62 level. Our results indicated that EGCG could recover the activity of autophagy in the TGF-ß1-treated cells. Moreover, treatments with EGCG significantly decreased the α-SMA expression. Taken together, these findings revealed that autophagic regulation involved in the action of EGCG against TGF-ß1-induced transformation of Tenon's fibroblasts. Through increasing intracellular autophagy, EGCG could be a potential anti-fibrotic reagent for preventing subconjunctival fibrosis after glaucoma filtration surgery.


Assuntos
Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Catequina/análogos & derivados , Miofibroblastos/efeitos dos fármacos , Cápsula de Tenon/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Actinas/metabolismo , Adenoviridae/genética , Western Blotting , Catequina/farmacologia , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/ultraestrutura , Proteína Sequestossoma-1/metabolismo , Cápsula de Tenon/metabolismo , Cápsula de Tenon/ultraestrutura , Transfecção , Fator de Crescimento Transformador beta1/antagonistas & inibidores
2.
Exp Eye Res ; 197: 108119, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32603658

RESUMO

Myofibroblast transformation of human Tenon's fibroblasts severely challenges the outcome of glaucoma filtration surgery. epigallocatechin-3-gallate (EGCG) is considered as a potential reagent to overcome this issue for its anti-fibrosis effect on various human diseases, but it is unclear on the fibrosis of Tenon's fibroblasts. This study was conducted to investigate the effect of EGCG on TGF-ß1-induced myofibroblast transformation of human Tenon's fibroblasts. The human Tenon's fibroblasts were incubated in the medium containing 10 ng/mL TGF-ß1, and subsequently treated with EGCG or mitomycin C (MMC). The cell proliferation and migration were analyzed. The expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col-I), and p-Smad2/3 were also evaluated. It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF-ß1 alone. Scratch-Wound assay showed that 48 h after TGF-ß1 induction, only 10% of the wound width remained. But cells treated with EGCG still showed over 93% wound width. Further, EGCG effectively inhibited TGF-ß1-induced expression of α-SMA and Col-I as well as phosphorylation of Smad2/3 in Tenon's fibroblasts. Altogether, we concluded that EGCG suppressed the myofibroblast transformation in Tenon's fibroblasts through inactivating TGF-ß1/Smad signaling. These findings demonstrate that EGCG can be considered as one of the possible antifibrotic reagents for preventing postoperative scarring in glaucoma filtration surgery.


Assuntos
Catequina/análogos & derivados , Glaucoma/tratamento farmacológico , Miofibroblastos/metabolismo , Cápsula de Tenon/metabolismo , Catequina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Glaucoma/metabolismo , Glaucoma/patologia , Humanos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Fármacos Neuroprotetores/farmacologia , Inibidores de Proteases , Transdução de Sinais , Cápsula de Tenon/efeitos dos fármacos , Cápsula de Tenon/patologia
3.
Clin Exp Ophthalmol ; 48(9): 1183-1191, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32713071

RESUMO

IMPORTANCE: Age-related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive. BACKGROUND: To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC). DESIGN: Retrospective study and experimental investigation. PARTICIPANTS: A total of 180 patients with PSC or non-PSC were included. METHODS: Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated. MAIN OUTCOME MEASURES: Aqueous humour UA and urate deposits. RESULTS: The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non-PSC. Treatment with UA-induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC. CONCLUSIONS AND RELEVANCE: These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.


Assuntos
Catarata , Cristalino , Humor Aquoso , Humanos , Estudos Retrospectivos , Ácido Úrico
4.
J Ophthalmol ; 2020: 6974202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802489

RESUMO

PURPOSE: To compare ocular anatomy differences of lens subluxation between eyes with or without acute angle closure (AAC). METHODS: This is a retrospective and case-control study. Sixty cases with mild lens subluxation were recruited. Among them, 30 eyes with acute angle closure were assigned to the AAC group and 30 eyes without AAC were assigned to the non-AAC group. The anterior segment was quantitatively evaluated by ultrasound biomicroscopy (UBM). The axial length (AL) was measured with IOL Master. All patients underwent lens extraction surgery and were followed up for six months. RESULTS: The history of blunt trauma accounted for 22 (73.3%) cases in the AAC group and 21 (70%) cases in the non-AAC group. Fifteen (50%) patients in the AAC group had iridotomy history, and high intraocular pressure recurred. The UBM analysis showed that the average central chamber depth of the affected eyes in the AAC group was 1.82 mm, which was significantly shallower than that in the fellow eyes (2.58 mm, P < 0.05) or both eyes in the non-AAC group.Both eyes in the AAC group presented a shorter AL and shallower anterior chamber than the eyes in the non-AAC group. CONCLUSIONS: An asymmetrical anterior chamber between bilateral eyes is an important feature in lens subluxation-induced AAC. The crowded anterior chamber and shorter AL might be the anatomic basis for the eye with lens subluxation-induced AAC.

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