Further-comprehension-of-eye-protective-layer-leads-to-paths-for-corneal-damage-and-disease-treatments

 

Denver, Colo.—Four novel studies presented this week at the Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting in Denver, Colo. explore multifaceted methods in healing damaged corneas. All studies show that the answers are already in that protective layer known as the cornea and that further research is needed to understand what else it is capable of. The hopes of the studies: that their results may lead to cost-effective, less invasive, and more efficient treatments for patients.

Non-surgical alternate therapy shows positive results in treating keratoconus

Lead researcher Nithan Kiran, MSc and fellow researchers at the Narayana Nethralaya Foundation and Narayana Nethralaya eye hospital in India studied the role of alternative treatments in slowing the progression of keratoconus (KC). The present treatment for end stage KC is corneal transplant surgery which is a financial burden to patients in the working class. The surgery poses other socioeconomic threats to this population as well.

“Keratoconus is characterised by progressive stromal thinning and weakness which leads to visual compromise.” said Kiran, “Inflammatory signalling, reduction of collagen crosslinking enzyme Lysyl Oxidase (LOX) and increased matrix metalloproteinase MMP9 have been found in patient corneas and tears.” Thus, Kiran and his team tested out an inflammation regulator Trehalose (TRE) and an MMP inhibitor Batimastat (BST) to see if they could rescue the LOX expression and block inflammatory signaling.

They used “corneal stromal lenticules from donors” that underwent small incision lenticule extraction (SMILE) refractive surgeries and treated them with BST and TRE for three weeks. They also monitored them under chronic inflammatory stress.  Kiran said that they “found that blocking inflammation and MMP9 in corneal cells or tissues rescued the LOX expression as well as collagens. Thus, using these drugs in keratoconus corneas might reactivate LOX expression leading to stabilisation of the corneal stroma and prevent progression of disease.” This alternate therapy would also be more feasible for the working class since it's non-invasive and potent.

• Abstract title: Rescue of Lysyl Oxidase levels by Batimastat and Trehalose treatment in human corneal stromal tissue and cell models: Implications for Keratoconus therapy
• Presentation start/end time: Wednesday, May 4, 4:25 – 4:42pm MT
• Location: 2A/3A Mile High Blrm (Denver Convention Center)
• Also available on the virtual meeting site at https://arvo2022.arvo.org/ beginning May 11
• Abstract Number: 4255

New findings suggest factors contributing to herpes simplex keratitis resurgence

Previous research relating to herpes simplex keratitis (HSK) primarily focused on corneal stromal cells, corneal epithelial cells, or the whole cornea structure. Researchers from Nanjing University in China redirected the focus onto corneal nerves “and in vitro cultured trigeminal ganglion” (TG) neurons, including unveiling pertinent cellular receptors and fundamental mechanisms.

Chenchen Wang, MD, PhD, and her group performed immunofluorescence on corneal nerves of healthy mice. This was used to identify the expression and distribution of herpes simplex virus type 1 (HSV-1) entry receptors in the nerves. They used quantitative real-time Polymerase Chain Reaction (qPCR) to evaluate the expression of HSV-1 receptors in TG in HSK and healthy mice.

They found the expression of HSV-1 entry receptors in healthy corneal nerves. Wang said, “The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence.” This data suggests “that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.” Wang also believed that this is the first study to establish NMHC-IIB and nectin-1 as key receptors facilitating the HSV-1 entry into corneal nerves “both in vivo and in vitro.”

• Abstract title: Nectin-1 and NMHC-IIB: major mediators of HSV-1 entry into corneal nerves
• Presentation start/end time: Wednesday, May 4, 12:30 – 2:30pm MT
• Location: Virtual (https://arvo2022.arvo.org/)
• Abstract Number: 3966 – A0246

Steven’s Johnson’s Syndrome and the IKZF1 Gene

Steven’s Johnson’s Syndrome (SJS) is a rare and serious illness that affects the mucous membrane, skin, eyes, and genitals. It is a severe immunological reaction that leads to an extreme inflammatory outbreak causing both visually and non-visually impairing eye issues. Researchers from Kyoto Furitsu Ika Daigaku (Kyoto Prefectural University of Medicine) in Japan and the Duke University Foster Center for Ocular Immunology Department of Ophthalmology worked together to have a better understanding of the immune physiopathology of SJS that could potentially point them in the right direction for new effective therapies.

In a collaborative effort to combine genetic and immunological studies, first Mayumi Ueta MD, PhD, and Shigeru Kinoshita, MD, PhD “were able to produce a novel mutant mouse strain with over-expression of an isoform of the IKZF1 gene which, in humans, was found to be associated with cold-medicine SJS.” Using this finding, lead researchers Victor L. Perez, MD, Daniel Saban, PhD, and team at the Foster Center for Ocular Immunology to join forces with the Kyoto Prefectural to evaluate eye changes and disease development between normal mice and IKZF1 transgenic mice (IK-Tg). They generated an immune challenge that was aligned with “the immune stimulus that induces SJS in humans.” They followed the allergic eye disease (AED) model for this challenge.

Perez, Saban, and team found that the IK-Tg mice had a stronger eye disease reaction in comparison to the normal mice. Perez said that the IK-Tg mice “are characterized by a unique disease phenotype that responds distinctly to an immune challenge resulting in added exaggeration of ocular disease. These mice can potentially be used to model the hypersensitivity of ocular inflammatory disorders, particularly Stevens-Johnson syndrome, allowing for a better grasp of the immune pathophysiology and identifying therapeutic targets in these conditions."

• Abstract title: Robust ocular inflammatory response to an immune allergic eye disease challenge in a novel murine IKZF1 transgenic model associated with Steven’s Johnson’s Syndrome
• Presentation start/end time: Sunday, May 1, 5:15 – 7:15pm MT
• Location: Poster Hall (Denver Convention Center/Virtual) Also available on the virtual meeting site at https://arvo2022.arvo.org/ beginning May 1
• Abstract Number: A0258

Reversing corneal myofibroblast: prospective approach in treating corneal scarring

When trauma to the eye transpires, vision impairment and corneal opacity occurs. This is due to the extensive formation and presence of wound repairing opaque cells in the stroma known as myofibroblasts. After an injury, myofibroblasts are created by corneal keratocytes to handle wound repair and then are supposed to leave after the wound closes. However, they are quite persistent once the wound closes, this causes more issues such as scarring and blindness.

Rajiv R. Mohan, MSc, PhD, FARVO, and a group of researchers from the University of Missouri System and Truman Memorial Veterans’ Hospital Columbia Missouri studied if corneal myofibroblasts could be de-differentiated, reversed, into precursor fibroblasts, keratocytes, through epigenetic reprogramming by sodium butyrate (NaB). NaB is “an epigenetic modifier and histone deacetylase inhibitor”. In addition, they wanted to test if it would restore corneal clarity.

The researchers collected primary human corneal stromal fibroblasts (hCSFs) produced from healthy donated corneas. They exposed the cultures to transforming growth factor beta1 (TGFβ1; 5 µg/mL) for 72 hours to create human corneal myofibroblasts (hCMFs). Then they effectuated epigenetic reprogramming for 72 hours.

They found that the corneal myofibroblasts were able to be reversed to keratocytes through epigenetic reprogramming with NaB. This is the first “research in abstract” to show “potential of reverting corneal myofibroblast to fibroblast.” said Mohan, “Identification of a novel epigenetic mechanism allowing conversion of opaque cells (myofibroblast) to transparent cells in cornea is highly significant and can potentially lead to novel non-surgical drug therapies to restore vision in humans and companion animals. Presently, corneal transplant surgery is a standard of care to remove corneal scar and restore vision in humans.”

• Abstract title: Epigenetic mechanism to induce dedifferentiation of corneal myofibroblast to fibroblast
• Presentation start/end time: Tuesday, May 3, 1:51 – 2:08pm MT
• Location: 2A/3A Mile High Blrm (Denver Convention Center)
• Also available on the virtual meeting site at https://arvo2022.arvo.org/ beginning May 11
• Abstract Number: 2640

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The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include approximately 10,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders. Learn more at ARVO.org.

The 2022 ARVO Annual Meeting will take place in Denver, Colo. from May 1 – 4 and virtually May 11 - 12. The Meeting is the premiere gathering of nearly 10,000 eye and vision researchers from around the world. During the Meeting, 4,800 abstracts will be presented on the latest basic and translational research in eye and vision science.

All abstracts accepted for presentation at the Annual Meeting represent previously unpublished data and conclusions. This research may be proprietary or may have been submitted for journal publication. Embargo policy: Journalists must seek approval from the presenter(s) before reporting data from paper or poster presentations. Press releases or stories on information presented at the ARVO Annual Meeting may not be released or published until the following embargo dates:

• May 1: Official launch of presentations of all posters (both presented in-person and virtually)
• Rolling basis: Paper session, Symposia, Minisymposia, Cross-sectional Groups, and invited speaker sessions that have specific presentation times will be embargoed until the end of those individual time slots.

Media contact:
Jenniffer Scherhaufer
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