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Sumana R Chintalapudi, Liyuan Li, Huiling Li, Mallika Palamoor, Xiaofei Wang, Vanessa Marie Morales, Monica M Jablonski; Identification of NA3 glycan as a potential candidate for atrophic AMD by promoting the development of photoreceptor outer segment assembly via receptor ligation in Müller cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2295.
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Atrophic Age-related Macular Degeneration is the most common type of AMD, accounting for approximately 90% of all cases, yet there is no available therapy. Atrophic AMD is characterized by damage to the macula, affecting the support of photoreceptors and ultimately, visual function. Our lab previously showed lactose and structurally related glycans support the photoreceptor outer segments (OS) in the absence of retinal pigment epithelium (RPE). The present study identifies the responsible glycan receptor and investigates its potential therapeutic use.
We evaluated the ultrastructure of OS in X. laevis embryos after RPE removal. Eyes were cultured under different glycan conditions to evaluate function, effective dose and treatment. NA3 binding affinity against competing glycans was assessed by immunohistochemistry analysis and flow cytometry in primary murine cells. Human retinae sections were also evaluated for NA3 binding affinity by IHC. In vivo binding pattern was analyzed in NZW rabbits by autoradiography.
We have demonstrated for the first time NA3 supports photoreceptor OS assembly with high affinity via receptor mediated response. This glycan does not alter structure or protein expression patterns in photoreceptors or Müller cells in the absence of RPE. FACS and immunostaining studies reveal NA3 binds to Müller cells. Results were consistent among the three species (Xenopus, mice and human). In vivo work in NZW rabbits confirmed these results, demonstrating NA3 binds to Müller cells.
We identified NA3 amongst different potential glycan candidates as a potential novel therapy for atrophic AMD by promoting the development of photoreceptor OS without altering other retinal structures.
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