Background To assess bioactive transforming growth factor-β2 (TGFβ2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma. Methods AH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGFβ2 and SFRP1 levels were assayed by ELISA. Results The concentration of TGFβ2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGFβ2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGFβ2 of AACG patients with high IOP (> 21 mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGFβ2 and SFRP1 did not correlate significantly with each other, or with age. Conclusions These results indicate that AH levels of TGFβ2 and SFRP1 showed different profiles in different types of glaucomas. Electronic supplementary material The online version of this article (10.1186/s12886-019-1183-1) contains supplementary material, which is available to authorized users.
PURPOSE. Excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) reduces aqueous humor outflow, which likely contributes to elevation of IOP in primary open-angle glaucoma (POAG). Salidroside, a phenolic glycoside isolated from Rhodiola rosea is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-b in liver, lung, and kidney tissues. We tested if salidroside can (1) inhibit TGF-b2induced ECM expression in cultured human TM cells, and (2) lower TGF-b2-induced ocular hypertension in the mouse. METHODS. Cultured human TM cells stimulated with 5 ng/mL TGF-b2 for 48 hours were treated with salidroside for 24 hours. The expressions of fibronectin (FN), collagen type IV (COL-IV), and laminin (LN) were evaluated by quantitative PCR, Western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGF-b2 (Ad.hTGF-b2 226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eyes serving as controls. Mice were treated with a daily intraperitoneal injection of 40 mg/kg salidroside. Conscious mouse IOP values were measured using a TonoLab rebound tonometer. RESULTS. In cultured human TM cells, treatment with TGF-b2 increased expressions of FN, COL-IV, and LN, as assessed by quantitative PCR, Western blotting, and immunocytochemistry, all of which were significantly and completely ameliorated by 30 lM salidroside. Daily intraperitoneal injections of salidroside (40 mg/kg), starting either at day 0 (same day as Ad.hTGF-b2 226/228 injection) or at day 14, significantly lowered TGF-b2-induced ocular hypertension in the mouse. In contrast, salidroside did not affect IOP of control eyes. CONCLUSIONS. These results demonstrated that salidroside is capable of minimizing TGF-b2induced ECM expression in cultured human TM cells. It also reduced TGF-b2-induced ocular hypertension in the mouse. These findings indicate that this phenolic glycoside may be useful as a novel treatment for POAG.
Elevation of IOP in POAG is thought to involve excessive accumulation of extracellular matrix in the trabecular meshwork (TM), leading to an increase in outflow resistance of the aqueous humor. Osthole, a coumarin derivative extracted from the fruit of a variety of plants, such as Cnidium monnieri, is reported to prevent profibrotic responses by inhibiting Smad signaling pathway activated by TGF-β in liver, kidney, and cardiac tissues. We tested if osthole can (1) inhibit TGF-β2-induced extracellular matrix expression in cultured human TM (HTM) cells, and (2) lower TGF-β2-induced ocular hypertension in the mouse. METHODS. Cultured HTM cells were treated with 5 ng/mL TGF-β2 for 48 hours, then with osthole for 24 hours. The expressions of fibronectin, collagen type IV, and laminin were assessed by quantitative PCR, Western blot, and immunocytochemistry. BALB/cJ mice were injected intravitreally with an adenoviral vector encoding a bioactive mutant of TGF-β2 (Ad.hTGF-β2 226/228) in one eye to induce ocular hypertension, with the uninjected contralateral or Ad.Empty-injected eye serving as controls. Mice were then treated with a daily intraperitoneal injection of 30 mg/kg osthole. Conscious mouse IOP values were measured using a TonoLab rebound tonometer. RESULTS. In cultured HTM cells, stimulation with TGF-β2 increased expressions of fibronectin, collagen IV, and laminin. These in vitro changes were significantly and completely mitigated by osthole (10 μM). Daily intraperitoneal injections of 30 mg/kg osthole, starting either at day 0 (same day as Ad.hTGF-β2226/228 injection) or at day 14, significantly decreased TGF-β2-induced ocular hypertension in the mouse. In contrast, osthole did not affect IOP of control eyes. CONCLUSIONS. These results demonstrated that osthole is capable of reducing TGF-β2-induced extracellular matrix expression in cultured HTM cells. It also reduced TGF-β2-induced ocular hypertension in the mouse. These findings indicate that this natural product may be useful as a novel treatment for POAG.
Background: Currently, there is no ideal material available for posterior scleral reinforcement (PSR) to prevent the progression of high myopia. In this study, we investigated robust regenerated silk fibroin (RSF) hydrogels as potential grafts for PSR in animal experiments to evaluate their safety and biological reactions.Methods: PSR surgery was performed on the right eye of twenty-eight adult New Zealand white rabbits, with the left eye serving as a self-control. Ten rabbits were observed for 3 months, while 18 rabbits were observed for 6 months. The rabbits were evaluated using intraocular pressure (IOP), anterior segment and fundus photography, A- and B-ultrasound, optical coherence tomography (OCT), histology, and biomechanical tests.Results: No complications such as significant IOP fluctuation, anterior chamber inflammation, vitreous opacity, retinal lesion, infection, or material exposure were observed. Furthermore, no evidence of pathological changes in the optic nerve and retina, or structural abnormalities on OCT, were found. The RSF grafts were appropriately located at the posterior sclera and enclosed in fibrous capsules. The scleral thickness and collagen fiber content of the treated eyes increased after surgery. The ultimate stress of the reinforced sclera increased by 30.7%, and the elastic modulus increased by 33.0% compared to those of the control eyes at 6 months after surgery.Conclusion: Robust RSF hydrogels exhibited good biocompatibility and promoted the formation of fibrous capsules at the posterior sclera in vivo. The biomechanical properties of the reinforced sclera were strengthened. These findings suggest that RSF hydrogel is a potential material for PSR.
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