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Narender K. Dhingra, Varsha Jain, Revathy Guruswamy; M1 Type of Intrinsically-Photosensitive Retinal Ganglion Cells Express Brn3 Transcription Factors in rd1 Mouse. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3458.
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We have previously found in wild-type retina that the non-M1, but not the M1 type of intrinsically-photosensitive retinal ganglion cells (ipRGCs) express brn3 transcription factors. We asked whether similar pattern of brn3 expression exists after photoreceptor loss in rd1 mouse retina.
Retinas of two adult rd1 mice (3 months and 2 years) were flat-mounted and immunofluorescently labeled for brn3 and melanoposin. The staining intensity and soma diameter of melanopsin cells were measured using ImageJ software to differentiate between M1 and non-M1 cells.
We found 1537 melanopsin cells (density: 146 cells per mm2) in the 3-month old rd1 mouse, while the number was 459 (55 cells per mm2) in the 2-year old rd1 mouse. In both retinas, approximately 30% of the melanopsin cells were two- to three-fold more brightly labeled than the remaining melanopsin cells. The soma diameter of the brightly labeled cells (15.3±0.2 µm) was significantly smaller than the faintly-labeled melanopsin cells (18.1 ± 1.4 µm). These data suggested that the relatively small, brightly-labeled cells were M1 type of ipRGCs. Although the absolute number of melanopsin cells in rd1 retina was different from that in wild-type mouse, the ratio of M1 to non-M1 cells was unaltered. Compared to the wild-type mouse where 95% of the non-M1 cells but only 14% of the M1 cells expressed brn3, in rd1 mice (both 3 months and 2 years old) approximately 98% of the non-M1 cells and >80% of the M1 cells expressed brn3. Overall, approximately 93% of all melanopsin cells in rd1 retina expressed brn3, whereas this value for the wild-type mouse was ~65%.
These results clearly demonstrate that the M1 cells, which do not express brn3 transcription factors in a wild-type mouse, express brn3 after photoreceptor loss in rd1 mouse. In a wild-type mouse retina, the expression of brn3 transcription factors in the M1 type of ipRGCs may be inhibited by photoreceptors.
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