INNOVATION OPTIC NERVE REGENERATION detachments that involve the optic nerve and the neural pathways too,” said Dr. Nakamura. “Trauma, other mechanical influences or inflammation, growth, neurotrophic and other factors, are far advanced options to think about aiming at visual restoration through nerve regeneration,” he added. Recent studies, according to Dr. Nakamura, have shown that for the successful restoration of vision, retinal ganglion cells would have to be present and healthy. “Also, their axons should grow to specific sites at the damaged areas and at the brain, as well, so as to enable the function of specific targets in the brain and making functional synaptic circuits available. Combination therapy involving cAMP also plays a role,” he added. “More often we get trapped and end up asking for visually evoked responses in order to track the visual pathway. But that is usually just a palliative measure to find out whether there’s any response from the patient to predict a usually poor outcome,” said Dr. Nakamura. “So that when we think of other retina capabilities in animals, such that of in zebrafish and frogs, we come to a better understanding of the pathways we could possibly involve in the human retina with that knowledge,” he explained. Currently however, in terms of vitreoretinal surgery, retinal specialists, according to Dr. Nakamura, still end up manipulating the retinal layers. For example, in the ILM (internal limiting membrane) folding technique for large macular holes: “The ILM autologous graft is transported towards the macular hole to actually fill in the hole defect and allow the ILM to grow over a new scaffold tissue to proliferate filling in the missing retina defect. This may grow a normal retina with its neural ganglion cell layers,” shared Dr. Nakamura. “Considering a normal eye anatomy and the different appearance of the ILM, the ILM forms the innermost boundary of the retina,” emphasized Dr. Nakamura. The outer retinal surface of this membrane is uneven and is
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Trauma, other mechanical influences or inflammation, growth, neurotrophic and other factors, are far advanced options to think about aiming at visual restoration through nerve regeneration.
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– Dr. Hudson de Carvalho Nakamura composed of extensive, expanded terminations of Müller cells (often called footplates) covered by a basement membrane. Anteriorly, the internal limiting membrane of the retina is continuous with the internal limiting membrane of the ciliary body. “It is present over the macula but undergoes modification at the optic disc, where processes from astrocytes replace those of the Müller cells. Type Ib astrocytes populate the nerve fiber layer and form the inner limiting membrane, serving as a barrier between the retina and the vitreous,” he added. “Therefore, if we think of Müller cell fragments inserted inside the hole, that could well support macular hole closure by inducing glial cell proliferation,” said Dr. Nakamura. “The process would create a scaffold for tissue proliferation in a larger manner because we are putting more substance inside the hole,” he explained.
Since a basement membrane is required for cell proliferation, that hypothesis, highlighted Dr. Nakamura, agrees with histopathologic findings, that the ILM, being a basement membrane, allows glial cell proliferation, and large macular holes will fill with tissue over time. “If we could ‘turn back the clock’, we could possibly make retinal regeneration feasible in glaucoma or trauma cases,” said Dr. Nakamura. “The fish and frog models are for sure teaching us on that subject and we need to learn more,” he advised. For the time being, according to Dr. Nakamura, while many other approaches are being tested, nothing is known for sure about definite results. “Results are coming in slowly, but despite some good results – for example in the field of retinal pigment epithelium transplant and amniotic membrane graft – we are not sure yet if we can link all these mentioned procedures to optic nerve regeneration,” he explained. “There are still questions that we don’t know the answer to, like the top of the new outer retina . . . could that be a place for retinal cell growth instead? That’s also a good question, but we don’t know as of yet,” concluded Dr. Nakamura. Editor’s Note: Dr. Nakamura was not involved in the study discussed in this article but was generous enough to share his expert opinion on the matter.
*Yin Y, De Lima S, Gilbert HY, et al. Optic nerve regeneration: A long view. Restor Neurol Neurosci. 2019 October [Epub ahead of print]
About the Contributing Doctor Hudson de Carvalho Nakamura, MD is an ophthalmologist specializing in the retina and vitreous. He completed his medical degree from School of Medicine at the Federal University of Goiás – UFG and residency from the Base Hospital of the Federal District - Brasília - DF. Presently, Dr. Nakamura is a member of the American Academy of Ophthalmology (AAO), Brazilian Council of Ophthalmology, Canadian Society of Ophthalmology and The Association for Research in Vision and Ophthalmology (ARVO). He currently works as a professor in the Department of Retina and Vitreous Course of Medical Residency in Ophthalmology at the Bank of Goias Eye Foundation and holds a vitreoretinal disease fellowship from the University of Toronto Canada and the Brazilian Center for Eye Surgery. [Email: hudson.nakamura@gmail.com]
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