Evaluation of Chitosan/Aptamer Targeting TGF-β Receptor II Thermo-Sensitive Gel for Scarring in Rat Glaucoma Filtration Surgery

Zhu, Xiaoyan; Xu, Duo; Zhu, Xiaomin; Li, Lei; Li, Haijun; Guo, Feng; Chen, Xia; Tan, Yan; Xie, Lin

doi:10.1167/iovs.15-16683

Cited by 27 publications

(15 citation statements)

References 32 publications

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“…Previous observations have indicated that TGF-β2 concentration is significantly higher in patients with either open-angle glaucoma (OAG) or POAG [11], which mark TGF-β2 as a novel therapeutic target for POAG. In fact, targeting TGF-β isoforms and/or related receptors has proven promising therapeutic targets in a glaucoma animal model [25]. For instance, in a rabbit model of glaucoma filtration surgery, subconjunctival injection of anti-TGF-β2 antibody CAT-152 significantly improved glaucoma surgery outcomes and reduced scarring [26].…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

Yang

Abdulatef

Zhang³

et al. 2020

Int. J. Med. Sci.

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Objective: To identify the interaction between the MYOC Y437H mutation and TGF-β2 in a family with primary open-angle glaucoma (POAG). Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-β2 found in the aqueous humor. Samples were taken both from normal controls and MYOC mutant carriers and cross-talk between MYOC Y437H and TGF-β2 were evaluated in the trabecular meshwork (TM) cells. Results: Aqueous humor secreted myocilin protein levels were reduced while TGF-β2 levels were increased in patients with the MYOC (c.1309T>C) mutation. This inverse relationship indicated that elevated TGF-β2 may be an important pathogenic mechanism in the progression of myocilin-related POAG. In TM cells expressing the MYOC Y437H mutant, exogenous TGF-β2 also significantly increased myocilin expression as well as the endoplasmic reticulum (ER) stress markers GRP94 and CHOP. This increase in TGF-β2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation. Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-β2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.

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Section: Discussionmentioning

confidence: 99%

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

Yang

Abdulatef

Zhang³

et al. 2020

Int. J. Med. Sci.

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“…The IOP percentage (IOP%) was calculated as follows: IOP% = IOP operated /IOP unoperated [14]. The IOP% decreased markedly on day 5 in the control group and on day 3 in the DED group; then, it gradually increased over time in both groups.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Dry Eye Disease on Scar Formation in Rabbit Glaucoma Filtration Surgery

Hong¹,

Zhu²,

Zhang³

et al. 2017

IJMS

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The success rate of glaucoma filtration surgery is closely related to conjunctival inflammation, and the main mechanism of dry eye disease (DED) is inflammation. The aim of this study was to evaluate the effect of DED on bleb scar formation after rabbit glaucoma filtration surgery. Sixteen New Zealand white rabbits were randomly divided into control and DED groups. A DED model was induced by twice-daily topical administration of 0.1% benzalkonium chloride (BAC) drops for three weeks. Ocular examinations were performed to verify the DED model. Surgical effects were assessed, and histologic assessments were performed on the 28th postoperative day. Higher fluorescein staining scores, lower basal tear secretion levels and goblet cell counts, and increased interleukin 1β (IL-1β) levels were observed in the DED group. The DED eyes displayed significantly higher intraocular pressure (IOP)% on the 14th postoperative day; a smaller bleb area on days 14, 21 and 28; and a shorter bleb survival time. Moreover, proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (α-SMA) levels were significantly increased in the DED group. These results demonstrate that DED promotes filtering bleb scar formation and shortens bleb survival time; these effects may be mediated via IL-1β.

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“…The histologic features of scar tissue formation include enhanced fibroblast proliferation, synthesis and secretion of collagen, and deposition of extracellular matrix. 23 Therefore, the inhibition of fibroblasts in the surgical field may attenuate scar tissue formation. Cyclosporin A suppresses collagen expression in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Grooved Glaucoma Drainage Devices That Continuously Deliver Cyclosporine A Decrease Postsurgical Scar Formation in Rabbit Eyes

Dai

Sun

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Dai Z, Yu X, Sun J, Sun X. Grooved glaucoma drainage devices that continuously deliver cyclosporine A decrease postsurgical scar formation in rabbit eyes. Invest Ophthalmol Vis Sci. 2017;58:169258: -170158: . DOI: 10.1167 PURPOSE. To study the functional outcomes of filtration surgery by implanting improved glaucoma drainage devices (GDDs) comprising surface grooves and a composite coating of cyclosporine A (CsA) and PLGA in experimental rabbit eyes.METHODS. Improved GDDs were designed and prepared by modifying normal GDD with surface grooves and a CsA-PLGA composite coating. Normal GDDs, grooved GDDs (G-GDDs), and GGDDs with a CsA-PLGA composite coating (CsA@G-GDD) were implanted into 18 rabbit eyes (six eyes per group). The intraocular pressure (IOP), bleb survival time, bleb morphology, and anterior chamber reactions were assessed for up to 12 weeks after GDD implantation. The IOPs were compared statistically among the three groups. Bleb morphology was quantified using the Indiana Bleb Appearance Grading Scale. Anterior chamber radiography was performed to check whether the filtrating pathway was blocked, and determine the drainage time and diffusion area of the contrast agent. Hematoxylin and eosin staining and immunohistochemistry were conducted to assess how the GDDs slowed or prevented scar formation.RESULTS. The improved GDDs were successfully prepared and implanted in 18 rabbit eyes without severe surgical complications. Bleb survival time was significantly longer and IOP was significantly lower in the G-GDD and CsA@G-GDD groups compared with the GDD group (all, P < 0.001). Blebs were significantly higher in the CsA@G-GDD group than in the GDD and G-GDD groups (P ¼ 0.003). Anterior chamber radiography revealed more unobstructed filtration channels in the CsA@G-GDD group than in the GDD group (P ¼ 0.032). Postsurgical scar formation was less extensive in the G-GDD and CsA@G-GDD groups than in the GDD group.CONCLUSIONS. Compared with the normal GDDs, G-GDDs with a CsA-PLGA coating inhibited postsurgical scar formation and improved the surgical success rate, and might represent an alternative to existing glaucoma filtration devices.Keywords: glaucoma drainage devices, cyclosporine A, groove, filtration surgery, scar formation G laucoma is characterized by elevated intraocular pressure (IOP) and frequently causes optic neuropathy. If left untreated, it causes chronic progressive degeneration of retinal ganglion cells and visual field loss.1,2 The treatment of glaucoma typically begins with topical medications and then filtering surgeries. 3 Glaucoma filtration surgery seeks to achieve incomplete healing to allow the aqueous humor to escape the eye, unlike other surgical procedures in which complete wound healing is desired. 4 Unfortunately, IOP often increases after surgery owing to scar formation in the wound field. The success rate of trabeculectomy was reported to be 64.7% over 5 years in eyes with open-angle glaucoma. 5 In complicated cases, implantation of a glaucoma drainage device (GDD) is...

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Evaluation of Chitosan/Aptamer Targeting TGF-β Receptor II Thermo-Sensitive Gel for Scarring in Rat Glaucoma Filtration Surgery

Abstract: This study presents evidence that the antifibrotic effect of chitosan in combination with aptamer S58 is superior to chitosan alone in a rat GFS model. Chitosan/S58 gel may be considered to be a promising antifibrotic agent for a local drug therapy.

Cited by 27 publications

References 32 publications

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

The Effect of Dry Eye Disease on Scar Formation in Rabbit Glaucoma Filtration Surgery

Grooved Glaucoma Drainage Devices That Continuously Deliver Cyclosporine A Decrease Postsurgical Scar Formation in Rabbit Eyes

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