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Editors Selection IGR 15-4

Basic Research: In-vivo measurement of RGC degeneration

Comment by Chris Leung on:

24608 A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells, Raymond ID; Pool AL; Vila A et al., Visual Neuroscience, 2009; 1-13

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While examining the integrity of retinal ganglion cells (RGCs) is pivotal to investigation of neurodegeneration and neuroprotection in glaucoma, labeling the RGCs and developing a reliable model of experimental glaucoma could be technically challenging. Raymond et al. (1441) provide a detailed description of generating a strain of transgenic mice that offers the potential for long-term in-vivo assessment of progressive RGC degeneration in glaucoma. This animal strain was generated by congenic breeding of a Thy-1 CFP mouse line, which provides intrinsic fluorescent labeling of RGCs, and a DBA/2J mouse line, which develops pigmentary glaucoma.

Investigation of Thy-1 CFP DBA/2J mice may provide mechanistic insight of RGC degeneration in glaucoma and identify potential therapeutic windows to promote RGC survival

Although the idea of cross breeding these two mouse lines is not new and the Thy-1 CFP DBA/2J mice have been used to study the location of damage to RGCs in glaucoma (Howell, et al. J Cell Biol 2007; 179: 1523-1537), it is recognized that this study provides an in depth validation and characterization of CFP expression in the Thy-1 CFP DBA/2J retinas. Microsatellite marker analysis was performed to confirm the mouse line is predominately DBA/2J congenic. Different markers of RGCs (NF-L, NeuN, Brn3a, SMI32) and amacrine cells (HPC-1, ChAT) were tested for co-localization study with CFP expression. With the advent of various in-vivo imaging techniques (Leung, et al. Invest Ophthalmol Vis Sci 2008; 49: 4898-4902; Murata, et al. Invest Ophthalmol Vis Sci 2008; 49: 5546-5552 ; Walsh, et al. J Neurosci Methods 2008; 169: 214-221), the investigation of Thy-1 CFP DBA/2J mice may provide mechanistic insight of RGC degeneration in glaucoma and identify potential therapeutic windows to promote RGC survival, with the caveat that progressive deposition of iris pigments may disrupt media clarity and impede in-vivo imaging as the animals age.

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