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25 July 2020 | Issue #2
Of Stem Cells and Cell Regeneration in Treatment of Retinal Vascular Diseases by Joanna Lee
“We’re looking at you looking at our retinas and trying to learn more about facilitating retinal cell regenerative therapies in humans, although, we can tell you the answers aren’t exactly black and white. Isn’t that more exciting?” the zebras mulled.
Possibilities of cell regeneration and challenges, to audacious goals and new developments in retinal vascular disease treatment, make for exciting times ahead...
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ince some vertebrates like zebras, fish or salamanders can regenerate large parts of their retina after injury, the search has been on to nurture the same ability for human retinal cells. In the Retinal Cell Therapies Symposium, Dr. Steven Becker, head of the National Eye Institute’s (NEI) Office of Regenerative Medicine spoke about new imaging modalities for monitoring retinal disease, referring to NEI’s Audacious Goals Initiative (AGI) launched in 2012 with the aim to “regenerate neurons and their neural connections in the eye and visual system”. One of NEI’s three funded consortia in advancing stem cell-based therapies is to develop functional imaging technologies. There has been five NEI AGI Imaging Grant Awards given. First, Alfredo Dubra (Stanford University) is working on a suite of technologies that can enable the higher resolution monitoring of different cell types. Kris Palczewski (UC-Irvine) has been developing a two-photon ophthalmoscope for safe imaging of cells or tissues in human retina that may allow for early detection, monitoring and evaluation of treatments.
Austin Roorda (UC-Berkeley) is looking into wide-field interferometry to measure neural activity non-invasively by combining it with various imagebased eye tracking tools. Over at Washington University, Victor Song is developing diffusion functional magnetic resonance imaging (dfMRI) technologies that would allow access to optic nerve anatomy in glaucoma and optic nerve neuropathies and to identify any occurring regeneration. Lastly, David Williams (University of Rochester) is working on OCT and AOSLO (reflectance, offset aperture, and two-photon) with calcium indicators, different metabolic sensors and labelled precursor cells to see if vision restoration could be assessed as well. Dr. Becker hoped these imaging advances will give clinicians new tools for disease progression assessment as well as the further development of new functional outcome measures for clinical trials and accelerate therapies for patients. Since 2008, inducible progenitor stem cells (iPSCs) are made from individual subject’s blood or epithelial cells which create the possibility of personalized medicine, other than using embryonic stem cells. AGI program’s advisor Dr. Russell Van Gelder spoke on barriers facing cell replacement therapies.
One of the barriers is the improvement in correct cellular differentiation (some cell types currently are more easily differentiated than others). Another challenge is generating sufficient number of cells for transplantation, and establishing correct cell polarity and connectivity. Lastly, there is a need to ensure these cells don’t escape differentiation pathways to form tumors or hematomas. Other challenges include managing immune responses and regulatory hurdles (FDA, and Good Laboratory Practice [GLP]). In the Retinal Vascular Disease Symposium, Dr. J. Fernando Arevalo discussed his team’s multicenter study on intravitreal anti-VEGF injections for exudative retinal arterial macroaneuryms (RAM) for which there has never been an established therapy. The results indicated anti-VEGF injections to be effective, leading to a decrease in macular edema in RAM patients. Dr. Wael Alsakran (King Khaled Eye Specialist Hospital, Saudi Arabia) spoke about using intravitreal triamcinolone acetonide (IVTA) as an adjunctive therapy in advanced Coat’s disease with exudative retinal detachment (ERD) where 13 out of 17 eyes experienced success with IVTA and ablative therapy without requiring surgical drainage. There is improvement in VA and central macular thickness. Excitement hovers over the first ever application of deep learning to sickle cell hemoglobinopathy in terms of wide-field fundus images as Dr. Sophie Cai discussed in a presentation titled Deep Learning Detection of Sea Fan Neovascularization from Ultra-Widefield Fundus Images of Sickle Cell Hemoglobinopathy. Her team’s study contributes to currently what they esteem to be the largest existing database of ultrawidefield fundus images of sickle cell hemoglobinopathy. With further investigations and external validation, they’re expecting this system to improve automated screening for vision-threatening sickle cell retinopathy. Other exciting discussions in this session included Real-world Treatment Patterns in Patients with Macular Edema due to Retinal Vein Occlusion by Dr. Vrinda Hershberger, and how Norrin protein promotes VEGF modulation and healthy in situ retinal regeneration in retinal vascular disease.
