Article
Ophthalmology
Eimi Suzuki, Takayoshi Sumioka, Shizuya Saika, Masayasu Miyajima, Shingo Yasuda, Hiroki Iwanishi, Yukihisa Takada, Kana Ichikawa, Jhuwala Venkatakrishnan, Chia-Yang Liu, Winston Whei-Yang Kao, Yuka Okada
Summary: Loss of lumican perturbs the healing pattern of a penetrating incision in mouse corneal stroma, accompanied by suppression of myofibroblast generation.
Review
Immunology
James W. Reinhardt, Christopher K. Breuer
Summary: This review details past studies on fibrocytes, their findings, and discusses their strengths and limitations, aiming to identify opportunities for further investigation and promote best practices in future study design.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Ophthalmology
Steven E. Wilson, Lycia Pedral Sampaio, Thomas Michael Shiju, Rodrigo Carlos de Oliveira
Summary: The corneal stroma, when unwounded, is a simple tissue with few cell types. However, after corneal injury, significant changes in cellularity occur, with adjacent keratocytes undergoing apoptosis, and bone marrow-derived cells infiltrating the stroma. This process is driven by factors like TGF beta and PDGF, and can result in the generation of myofibroblasts and scarring fibrosis if the epithelial and basement barriers are not repaired or replaced in time.
EXPERIMENTAL EYE RESEARCH
(2021)
Review
Cell Biology
Steven E. Wilson
Summary: Fibrosis, a result of infections, injuries, or diseases, is the development of excessive fibrous tissue in organs. The cornea provides a unique model to study fibrosis response. Injury and defective regeneration trigger the development of myofibroblasts, which persist until the source of injury is removed. Similar mechanisms can be observed in other organs.
Article
Ophthalmology
Sabeeh Kamil, Rajiv R. Mohan
Summary: Corneal stromal wound healing is a complex process involving apoptosis, proliferation, migration, and transdifferentiation of keratocytes. The central player guiding stromal responses is TGF-beta signaling, while other major regulators include myofibroblasts, basement membrane, collagen fibrils, and small leucine-rich proteoglycans. Understanding the roles of these regulators has helped develop novel therapies to prevent corneal opacity.
Article
Cell Biology
Nishant R. R. Sinha, Ratnakar Tripathi, Praveen K. K. Balne, Laila Suleiman, Katherine Simkins, Shyam S. S. Chaurasia, Rajiv R. R. Mohan
Summary: Sulfur mustard gas is a chemical weapon that causes vesication and alkylation, leading to ocular injuries. This study investigated the role of the SMAD2/3 signaling pathway in corneal fibrosis induced by sulfur mustard gas exposure. The results showed that SMAD2/3 signaling is involved in the formation of myofibroblasts in the cornea following mustard gas exposure.
Review
Biochemistry & Molecular Biology
Steven E. Wilson
Summary: Bowman's layer is an acellular layer in the anterior stroma of the cornea. It does not significantly contribute to mechanical stability or act as a barrier. However, it represents ongoing cytokine and growth factor-mediated interactions between corneal epithelial cells and stromal keratocytes. The destruction of Bowman's layer is associated with certain eye diseases and the development of fibrovascular tissue in the cornea.
Review
Biochemistry & Molecular Biology
Steven E. E. Wilson
Summary: Mesenchymal cells and mesenchymal progenitor bone marrow-derived fibrocytes play a crucial role in stromal fibrosis after corneal injury. They have both anti-fibrotic and pro-fibrotic functions, such as regulating the effects of transforming growth factor, modulating the entry of bone marrow-derived cells, promoting corneal epithelial healing, and contributing to the regeneration of basement membranes. The balance between these functions is important in determining the outcome of tissue fibrosis.
Article
Multidisciplinary Sciences
Wentao Liang, Li Huang, Amy Whelchel, Tian Yuan, Xiang Ma, Rui Cheng, Yusuke Takahashi, Dimitrios Karamichos, Jian-Xing Ma
Summary: Diabetes impairs corneal wound healing through dysregulation of mitochondrial function. Downregulation of PPAR & alpha; is critical for impaired mitochondrial function and delayed corneal wound healing in diabetic cornea.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Liat Chaushu, Svetlana Atzil, Marilena Vered, Gavriel Chaushu, Shlomo Matalon, Evgeny Weinberg
Summary: Complete wound closure was faster in old rats, with a more dimensional related wound closure observed in young rats. Inflammatory response and myofibroblastic response were significantly delayed and of lower intensity in old rats, although not statistically significant. Reduced initial tissue damage in old rats led to faster clinical wound healing compared to young rats.
Review
Pharmacology & Pharmacy
Vishal Jhanji, Isabelle Billig, Gary Hin-Fai Yam
Summary: Corneal opacification is the fourth most common cause of blindness globally. The standard treatment for serious corneal scarring is corneal transplantation, but there are limitations such as long-term graft survival and the lifelong use of immunosuppressants. Research is focused on finding new technologies to modulate wound healing and prevent corneal opacification.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Pascale Desjardins, Gaetan Le-Bel, Sergio C. Ghio, Lucie Germain, Sylvain L. Guerin
Summary: This study elucidates the molecular mechanisms by which WNK1 contributes to corneal wound healing. By regulating the activity and expression of transcription factors, WNK1 can impact the transcription of multiple genes, thereby controlling the migration, proliferation, and differentiation of corneal epithelial cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Cristina Blanco-Elices, Carmen Morales-Alvarez, Jesus Chato-Astrain, Carmen Gonzalez-Gallardo, Paula Avila-Fernandez, Fernando Campos, Ramon Carmona, Miguel Angel Martin-Piedra, Ingrid Garzon, Miguel Alaminos
Summary: The purpose of this study was to determine the potential usefulness of heterotypic cornea substitutes generated with extra-corneal cells in tissue engineering. The stromal layer of these bioartificial corneas showed low levels of components of the tissue extracellular matrix ex vivo, but exhibited higher levels of maturation and spatial organization when grafted in vivo. The results suggest that these bioartificial corneas have the potential for future clinical use.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Immunology
Yuka Okada, Takayoshi Sumioka, Peter S. Reinach, Masayasu Miyajima, Shizuya Saika
Summary: Maintaining corneal transparency is crucial for normal vision, and the pathogenic responses during corneal wound healing can lead to opacification. Studies have shown that different transient receptor potential channel (TRP) isoforms play important roles in mediating the control of conventional ocular tissue under normal and pathological conditions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Anusha Balla, Bao Tran, Annika Valtari, Philipp Steven, Camilla Scarpellini, Koen Augustyns, Arto Urtti, Kati-Sisko Vellonen, Marika Ruponen
Summary: In this study, the positive effect of a novel ferroptosis inhibitor, UAMC-3203, on corneal epithelial wound healing was investigated using in vitro and ex vivo models. The drug solution at a concentration of 100 μM showed no toxicity when applied topically in rats for 5 days. Furthermore, the distribution of UAMC-3203 in the cornea revealed significantly higher concentration in the epithelium compared to the stroma.
Article
Ophthalmology
Rodrigo Carlos de Oliveira, Lycia Pedral Sampaio, Thomas Michael Shiju, Marcony R. Santhiago, Steven E. Wilson
Summary: The study aims to investigate EBM regeneration in non-fibrotic and fibrotic corneas after PRK. It was found that defective perlecan incorporation in fibrotic corneas can lead to incomplete EBM regeneration, while fully regenerated EBM in non-fibrotic corneas is associated with restoration of corneal transparency.
JOURNAL OF REFRACTIVE SURGERY
(2022)
Review
Cell Biology
Steven E. Wilson
Summary: Fibrosis, a result of infections, injuries, or diseases, is the development of excessive fibrous tissue in organs. The cornea provides a unique model to study fibrosis response. Injury and defective regeneration trigger the development of myofibroblasts, which persist until the source of injury is removed. Similar mechanisms can be observed in other organs.
Article
Ophthalmology
Lycia Pedral Sampaio, Guilherme S. L. Hilgert, Thomas Michael Shiju, Sofia E. Mueillo, Marcony R. Santhiago, Steven E. Wilson
Summary: The study showed that topical losartan can reduce central stromal opacity intensity, peripheral corneal scarring, and decrease alpha-smooth muscle actin myofibroblast fibrosis area. Additionally, topical losartan can also decrease posterior stromal cellular collagen type IV production.
EXPERIMENTAL EYE RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Steven E. Wilson, Thomas M. Shiju, Lycia Pedral Sampaio, Guilherme S. L. Hilgert
Summary: Collagen type IV plays a key role in controlling the pro-fibrotic effects of transforming growth factor beta. It binds TGF beta and regulates its function in various organs. Losartan, a known TGF beta signaling inhibitor, can alter the production of collagen type IV and potentially mitigate the effects of TGF beta. Similar pathways may exist in other organs as well.
Article
Ophthalmology
Lycia Pedral Sampaio, Guilherme S. L. Hilgert, Thomas Michael Shiju, Marcony R. Santhiago, Steven E. Wilson
Summary: This study evaluated the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits. The results showed that the combined use of these two drugs significantly reduced opacity area and intensity, decreased myofibroblast area and staining intensity, and confined myofibroblasts to the posterior stroma while promoting repopulation of the anterior and mid-stroma with keratocan-positive keratocytes. Furthermore, topical losartan reduced the production of collagen type IV. These findings suggest that topical losartan and prednisolone acetate can effectively decrease myofibroblast-mediated scarring fibrosis after corneal injury.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Correction
Ophthalmology
L. P. Sampaio, G. S. L. Hilgert, T. M. Shiju, M. R. Santhiago, S. E. Wilson
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Ophthalmology
Steven E. Wilson
Summary: For the treatment of corneal pathophysiology associated with epithelial healing disorders, stromal scarring fibrosis, corneal neovascularization, and corneal endothelial injury, several medications, such as nerve growth factor, losartan, tyrosine kinase inhibitors, and Rho-kinase inhibitors, have shown potential efficacy and are in various stages of clinical trials.
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2022)
Article
Ophthalmology
Amanda Luiza Pereira-Souza, Renato Ambrosio, Francisco Bandeira, Marcella Q. Salomao, Acacio Souza Lima, Steven E. Wilson
Summary: This case report highlights the first clinical experience with topical losartan for treating severe corneal haze after LASIK surgery. Following treatment, there was improvement in visual acuity and corneal condition. Topical losartan shows promise in treating corneal haze formation post corneal injuries.
JOURNAL OF REFRACTIVE SURGERY
(2022)
Review
Biochemistry & Molecular Biology
Steven E. E. Wilson
Summary: Mesenchymal cells and mesenchymal progenitor bone marrow-derived fibrocytes play a crucial role in stromal fibrosis after corneal injury. They have both anti-fibrotic and pro-fibrotic functions, such as regulating the effects of transforming growth factor, modulating the entry of bone marrow-derived cells, promoting corneal epithelial healing, and contributing to the regeneration of basement membranes. The balance between these functions is important in determining the outcome of tissue fibrosis.
Article
Ophthalmology
Valeria Villabona-Martinez, Lycia Pedral Sampaio, Thomas Michael Shiju, Steven E. Wilson
Summary: Alkali burns are commonly used in corneal wound healing studies. The extent of injury and fibrosis in the cornea depends on whether Descemet's membrane and the endothelium are injured during the initial exposure. A method using filter paper soaked in alkali solution for 15 seconds before irrigation in rabbit corneas showed that higher concentrations of NaOH led to more severe fibrosis and increased likelihood of corneal neovascularization and persistent epithelial defects.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Ophthalmology
Steven E. Wilson
Summary: Losartan, an angiotensin II receptor blocker, inhibits TGF beta signaling by blocking ERK activation. Studies have shown its efficacy in reducing scarring fibrosis in various eye injuries and complications. Clinical studies are needed to explore its effectiveness and safety in treating corneal scarring fibrosis and other eye diseases involving TGF beta. It has the potential to enhance pharmacological therapeutics for ocular diseases where TGF beta plays a central role.
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Steven E. Wilson
Summary: Bowman's layer is an acellular layer in the anterior stroma of the cornea. It does not significantly contribute to mechanical stability or act as a barrier. However, it represents ongoing cytokine and growth factor-mediated interactions between corneal epithelial cells and stromal keratocytes. The destruction of Bowman's layer is associated with certain eye diseases and the development of fibrovascular tissue in the cornea.
Article
Ophthalmology
Thomas Michael Shiju, Lycia Pedral Sampaio, Valeria Villabona Martinez, Guilherme S. L. Hilgert, Steven E. Wilson
Summary: The localization of TGF beta-3 in unwounded and injured rabbit corneas was evaluated, as well as its effects on corneal fibroblasts in vitro. TGF beta-3 was found to have a different distribution pattern compared to TGF beta-1 and TGF beta-2, but had similar effects to TGF beta-1 on corneal fibroblast development.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Ophthalmology
Steven E. Wilson
Summary: Corneal fibroblasts play a crucial role in wound healing, originating from keratocytes.Transforming growth factor (TGF)-01 and TGF02, along with platelet-derived growth factor (PDGF), regulate the transition of keratocytes to corneal fibroblasts.Coronal fibroblasts perform various functions in damaged cornea, including basement membrane (BM) regeneration, control of TGF0 effects on stromal cells, attraction of bone marrow-derived cells, modulation of epithelium regeneration, and contribution to stromal integrity.
Article
Biochemistry & Molecular Biology
Thomas Michael Shiju, Lycia Pedral Sampaio, Guilherme S. L. Hilgert, Steven E. Wilson
Summary: This study investigated the contribution of different cell types, alone or in combination, to the assembly of the epithelial basement membrane (BM) during corneal wound healing using a 3D corneal organotypic model and an in situ rabbit photorefractive keratectomy (PRK) model. The results showed that the corneal epithelial BM is formed by the coordination of epithelial cells and corneal fibroblasts, while no BM was observed in cultures of epithelial cells and myofibroblasts, corneal epithelial cells alone, or corneal fibroblasts alone.
Article
Ophthalmology
He-Yan Li, Li Dong, Xu-Han Shi, Rui-Heng Zhang, Wen-Da Zhou, Hao-Tian Wu, Chu-Yao Yu, Yi-Tong Li, Yi-Fan Li, Jost B. Jonas, Wen-Bin Wei, Yue-Ming Liu
Summary: This study aimed to examine the intraocular tolerability of cetuximab when applied intravitreally, and its effect on axial elongation. The results showed that intravitreal injections of cetuximab could reduce axial elongation in a dose-dependent and number of treatment-dependent manner, without causing intraocular toxic effects.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
James D. Cole, John A. McDaniel, Joelle Nilak, Ashley Ban, Carlos Rodriguez, Zuhaad Hameed, Marta Grannonico, Peter A. Netland, Hu Yang, Ignacio Provencio, Xiaorong Liu
Summary: Aniridia is a panocular condition characterized by the loss of iris, caused mainly by mutations in the PAX6 gene. This study assessed the effects of Pax6-haploinsufficiency on retinal morphology and vision in Pax6Sey mice. The results showed elevated intraocular pressure and declining visual acuity in Pax6Sey mice, along with local retinal damage and a possible neuroinflammatory response.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Subao Jiang, Ning Xia, Francesco Buonfiglio, Elsa W. Boehm, Qi Tang, Norbert Pfeiffer, Dominik Olinger, Huige Li, Adrian Gericke
Summary: This study found that a high-fat diet induces endothelial dysfunction in the ophthalmic artery, leading to impaired vascular function in the eye. The high-fat diet triggers oxidative stress and involves RAGE and NOX2.
EXPERIMENTAL EYE RESEARCH
(2024)
Review
Ophthalmology
Mala Upadhyay, Vera L. Bonilha
Summary: The sodium iodate (NaIO3) model is a valuable tool in studying dry AMD and evaluating the retinal structure. Through extensive research, it has been found that the death of RPE cells caused by NaIO3 injection is closely related to vision loss in patients with dry AMD. Therefore, studying NaIO3 can provide insights into the mechanisms of RPE and photoreceptor cell death and contribute to understanding RPE degeneration in AMD.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Vicki Chrysostomou, Katharina C. Bell, Sze Woei Ng, Samyuktha Suresh, Gayathri Karthik, Marion Millet, Yingying Chung, Jonathan G. Crowston
Summary: We present a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. This model allows for the reliable induction of RGC dysfunction and loss, with the resilience of the optic nerve being dependent on the age of the animal. The time-defined nature of the functional and structural changes observed in this model will facilitate the study of glial responses and the evaluation of neuroprotective treatments after intraocular pressure (IOP) injury.
EXPERIMENTAL EYE RESEARCH
(2024)
