Inflammatory factors cause damage to back of eye following keratoprosthesis implantation
- Date:
- April 7, 2016
- Source:
- Massachusetts Eye and Ear Infirmary
- Summary:
- Researchers have identified inflammatory factors that contribute to optic nerve damage following keratoprosthesis implantation in a mouse model, a new report outlines.
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Researchers from Massachusetts Eye and Ear/Harvard Medical School have identified inflammatory factors that cause optic neuropathy in the back of the eye following implantation of a keratoprosthesis (KPro) -- similar to what glaucoma patients experience, without the rise of pressure in the eye -- and have shown that blocking one of those factors, tumor necrosis factor alpha (TNFa), successfully halts the development of optic nerve damage in a mouse model. Their findings, published online in Investigative Ophthalmology and Visual Science, shed light on the underlying process responsible for optic neuropathy in KPro patients and also suggest a new pathway for preventing optic nerve damage in patients who receive the KPro implant.
"We used a mouse model of the KPro to, first of all, identify the inflammatory factors that cause damage to the eye, and then we also quantified the amount of nerve cell death in the back of the eye that mediates the optic neuropathy, and, lastly, we looked at blocking these factors with antibodies," said Reza Dana, M.D., M.Sc., MPH, Director of the Cornea and Refractive Surgery Service at Massachusetts Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. "We found that the KPro leads to high levels of TNFa, and that by blocking TNFa, we can prevent the nerve damage."
With more than 1,000 KPro surgeries performed annually, and with new technologies being developed to increase the number of patients who may benefit, the KPro is a clear, plastic artificial cornea often used to replace diseased corneas in patients prone to rejecting biological tissues. The vast majority of KPro recipients report good vision initially, and then later experience a progression of optic neuropathy -- damage to the optic nerve that carries signals from the back of the eye to the brain.
To better understand these responses in the eyes of KPro recipients, the researchers studied the effects of keratoprosthesis implantation in an animal model. They found that the mice can develop damage to the optic nerve despite normal pressure in the eye following KPro surgery and identified TNFa and IL-1 as inflammatory factors involved in this process, with high levels of TNFa mediating the damage to the optic nerve. The findings represent the first proof of concept regarding the role of TNFa as a result of keratoprosthesis surgery damaging the optic nerve.
"Now we have a much more mechanistic understanding the mediator behind this clinical presentation," Dr. Dana said. "Future studies are needed to prove that TNFa blocking can be therapeutic in humans, but in the meantime, this new knowledge clarifies the pathway to cell death of the optic nerve following KPro surgery."
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Materials provided by Massachusetts Eye and Ear Infirmary. Note: Content may be edited for style and length.
Journal Reference:
- Alja Crnej, Masahiro Omoto, Thomas H. Dohlman, Miguel Gonzalez-Andrades, Eleftherios I. Paschalis, Andrea Cruzat, T. H. Khanh Vu, Marianne Doorenbos, Dong Feng Chen, Claes H. Dohlman, Reza Dana. Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye. Investigative Opthalmology & Visual Science, 2016; 57 (4): 1643 DOI: 10.1167/iovs.15-17557
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