Michael B Powner1,2, Sasha M Woods1, Meidong Zhu3,4, Mark C Gillies3, Paul S Bernstein5, Gregory S Hageman6, Grant M Comer7, Catherine Egan8, Marcus Fruttiger1. 1. MacTel Research Group, UCL Institute of Ophthalmology, University College London, London, United Kingdom. 2. Applied Vision Research Centre, School of Health Sciences, City University London, London, United Kingdom. 3. Save Sight Institute, University of Sydney, Sydney, Australia. 4. Lions New South Wales Eye Bank, Sydney Eye Hospital, New South Wales Organ and Tissue Donation Service, Sydney, Australia. 5. Department of Ophthalmology and Visual Sciences, School of Medicine, Moran Eye Center, University of Utah, Salt Lake City, Utah. 6. Department of Ophthalmology and Visual Sciences, Sharon Eccles Steele Center for Macular Degeneration, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. 7. W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan. 8. MacTel Research Group, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
Abstract
PURPOSE: Macular telangiectasia Type 2 (MacTel) causes glial and photoreceptor cell death in a small, oval patch in the central retina. Beyond this oval area, no disease manifestations have been described so far. Here, we describe a novel pathological aspect of MacTel in the retinal pigment epithelium (RPE) that is not restricted to the clinically affected area but covers the entire retina. METHODS: We have studied postmortem eyes from four patients with MacTel by immunohistochemistry and electron microscopy. RESULTS: We found cellular debris in the subretinal space (between photoreceptor outer segments and RPE), consisting mainly of outer segments and RPE components. In healthy eyes, the RPE normally phagocytoses the tips of the continuously growing outer segments, a process considered to be essential for photoreceptor survival. However, in the patients with MacTel, we found no evidence of ongoing outer segment phagocytosis, and the apical surface of the RPE appeared abnormal throughout most of the retina. CONCLUSION: Reduced outer segment phagocytosis may explain the accumulating debris in the subretinal space but is a surprising finding because visual function in the peripheral retina is normal in patients with MacTel. Nevertheless, the subclinical pathology might induce a specific stress to which the central area is uniquely susceptible.
PURPOSE: Macular telangiectasia Type 2 (MacTel) causes glial and photoreceptor cell death in a small, oval patch in the central retina. Beyond this oval area, no disease manifestations have been described so far. Here, we describe a novel pathological aspect of MacTel in the retinal pigment epithelium (RPE) that is not restricted to the clinically affected area but covers the entire retina. METHODS: We have studied postmortem eyes from four patients with MacTel by immunohistochemistry and electron microscopy. RESULTS: We found cellular debris in the subretinal space (between photoreceptor outer segments and RPE), consisting mainly of outer segments and RPE components. In healthy eyes, the RPE normally phagocytoses the tips of the continuously growing outer segments, a process considered to be essential for photoreceptor survival. However, in the patients with MacTel, we found no evidence of ongoing outer segment phagocytosis, and the apical surface of the RPE appeared abnormal throughout most of the retina. CONCLUSION: Reduced outer segment phagocytosis may explain the accumulating debris in the subretinal space but is a surprising finding because visual function in the peripheral retina is normal in patients with MacTel. Nevertheless, the subclinical pathology might induce a specific stress to which the central area is uniquely susceptible.
Authors: Charles L Zucker; Paul S Bernstein; Richard L Schalek; Jeff W Lichtman; John E Dowling Journal: Proc Natl Acad Sci U S A Date: 2020-07-22 Impact factor: 11.205
Authors: Roberto Bonelli; Sasha M Woods; Brendan R E Ansell; Tjebo F C Heeren; Catherine A Egan; Kamron N Khan; Robyn Guymer; Jennifer Trombley; Martin Friedlander; Melanie Bahlo; Marcus Fruttiger Journal: Sci Rep Date: 2020-07-22 Impact factor: 4.379
Authors: Katie M Litts; Mali Okada; Tjebo F C Heeren; Angelos Kalitzeos; Vincent Rocco; Rebecca R Mastey; Navjit Singh; Thomas Kane; Melissa Kasilian; Marcus Fruttiger; Michel Michaelides; Joseph Carroll; Catherine Egan Journal: Transl Vis Sci Technol Date: 2020-03-30 Impact factor: 3.048