Scar formation in the presence of mitomycin C and the anti-fibrotic antibody in a rabbit model of glaucoma microsurgery: A pilot study

Shukla, Aakriti Garg; Milman, Tatyana; Fertala, Jolanta; Steplewski, Andrzej; Fertala, Andrzej

doi:10.1016/j.heliyon.2023.e15368

Cited by 3 publications

(7 citation statements)

References 50 publications

(64 reference statements)

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“…However, based on our recent study on using ACA to limit scar formation associated with glaucoma surgery, we already know that compared to mitomycin C, ACA offers some advantages. For instance, compared to mitomycin-C-treated injury, we observed a significantly lower number of profibrotic cross-links in the ACA-treated areas [27]. Further studies comparing ACA with 5-fluorouracil and mitomycin-C will show the advantages and disadvantages of different modes of reducing fibrosis in corneal scarring.…”

Section: Limitations and Clinical Implicationsmentioning

confidence: 72%

“…Our group has demonstrated that targeting collagen fibrillogenesis with ACA attenuates scar formation and does not cause any side effects in animal-based preclinical models of fibrotic scarring [22,27]. These earlier studies targeted posttraumatic scarring in tissues with a relatively low degree of collagen fibril organization.…”

Section: Antiscarring Aca To Treat Corneal Scarringmentioning

confidence: 99%

“…The present study focuses on scar neotissue formed after eight weeks in the incision wounds created in rabbit corneas. During this study, we also analyzed the effects of antifibrotic ACA on collagen-rich corneal scar tissue formation [20,22,27]. Utilizing microscopic and spectroscopic methods, we measured two crucial elements of the corneal stroma: collagen and PGs.…”

Section: Corneal Scarringmentioning

confidence: 99%

“…Five 5 µm thick sections were obtained at each level and stained with H&E, Masson's trichrome, or periodic acid-Schiff dyes. Additional unstained preparations were used to stain collagen fibrils with picrosirius red [27].…”

Section: Tissue Collectionmentioning

confidence: 99%

“…H&E-stained sections were analyzed blind by an ocular pathologist (T.M. ), who scored the anterior segment for the presence of inflammatory cells, vascularization, and the extent of fibrosis in the incision area [27]. In addition to H&E staining, the presence of blood vessels was confirmed with immunostaining using anti-αSMA antibodies, as we have described elsewhere [47].…”

Section: Histopathology Of the Eyesmentioning

confidence: 99%

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Corneal Wound Healing in the Presence of Antifibrotic Antibody Targeting Collagen Fibrillogenesis: A Pilot Study

Syed,

Milman,

Fertala

et al. 2023

IJMS

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Highly organized collagen fibrils interlacing with proteoglycans form the crucial architecture of the cornea and facilitate its transparency. Corneal scarring from accidental injury, surgery, or infection alters this highly organized tissue, causing severe consequences, including blindness. There are no pharmacological or surgical methods to effectively and safely treat excessive corneal scarring. Thus, we tested the anticorneal scarring utility of a rationally designed anticollagen antibody (ACA) whose antifibrotic effects have already been demonstrated in nonocular models. Utilizing a rabbit model with an incisional corneal wound, we analyzed ACA’s effects on forming collagen and proteoglycan-rich extracellular matrices in scar neotissue. We used microscopic and spectroscopic techniques to quantify these components and measure crucial parameters characterizing the structure and organization of collagen fibrils. Moreover, we analyzed the spatial distribution of collagen and proteoglycans in normal and healing corneas. Our study demonstrated significant changes in the quality and quantity of the analyzed molecules synthesized in scar neotissue. It showed that these changes extend beyond incision margins. It also showed ACA’s positive impact on some crucial parameters defining proper cornea structure. This pilot study provides a stepping stone for future tests of therapeutic approaches that target corneal extracellular scar matrix assembly.

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Section: Limitations and Clinical Implicationsmentioning

confidence: 72%

Section: Antiscarring Aca To Treat Corneal Scarringmentioning

confidence: 99%