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Fig. 7 | Journal of Neuroinflammation

Fig. 7

From: Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa

Fig. 7

Inhibition of the prostaglandin receptor EP2 by TG6-10-1 preserves photoreceptors in rd10 mice. ac A long stretch of a retinal section from P25 CX3CR1+/GFP (A) and rd10/CX3CR1+/GFP mice treated with TG6-10-1 (b) or DMSO (c) were stained an antibody against red/green opsins showing cone OS in WT mouse retinas (a, red) and cone OS and IS in rd10 mouse retinas (b, c, red). Cell nuclei were stained with DAPI (blue). df Retinal sections from the boxed regions in a, b, and c. ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer, GCL ganglion cell layer. gi Retinal flat from the dorsal retina at about 1 mm away from the optic nerve head along the dorsal-ventral axis of P25 CX3CR1+/GFP (g) and rd10/CX3CR1+/GFP mice treated with TG6-10-1 (h) or DMSO (i) were stained with an antibody against red/green opsins. The retina from WT mice shows red/green-opsin-expressing cone OSs (g, arrows in inset). Cone OS and IS in the retina of P25 rd10/CX3CR1+/GFP mice treated with TG6-10-1 remained partially intact (h, arrows in inset), whereas cone OS and IS in the retina of P25 rd10/CX3CR1+/GFP mice treated with DMSO were flattened (i, arrows in inset). j Average thickness of the ONL, measured in numbers of photoreceptor nuclear rows per column in retinal vertical sections (F(2, 15) = 160.69, p = 7.4 × 10−11; WT versus DMSO-treated rd10, p = 5.8 × 10−9; WT versus TG6-10-1 treated rd10, p = 1.2 × 10−7; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0016). k Average length of cone OS/IS, measured in retinal vertical sections (F(2, 15) = 51.88, p = 1.8 × 10−7; WT versus DMSO-treated rd10, p = 2.6 × 10−6; WT versus TG6-10-1 treated rd10, p = 4.6 × 10−5; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0015). Scale bars: 20 μm. l Quantification of cone cell densities from flat mounted retinas of P25 CX3CR1+/GFP and rd10/CX3CR1+/GFP mice treated with TG6-10-1 or DMSO (F(2, 15) = 78.82, p = 1.1 × 10−8; WT versus DMSO-treated rd10, p = 1.8 × 10−7; WT versus TG6-10-1 treated rd10, p = 9.8 × 10−7; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0017). m Scotopic ERG responses to 3 cd-s/m2 light intensity from P25 CX3CR1+/GFP WT and rd10/CX3CR1+/GFP mice treated with TG6-10-1 or DMSO. Statistical analysis of scotopic a-wave amplitudes (F(2, 15) = 38.21, p = 1.3 × 10−6; WT versus DMSO-treated rd10, p = 1.1 × 10−5; WT versus TG6-10-1 treated rd10, p = 0.00017; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0015), and b-wave amplitudes (F (2, 15) = 123.23, p = 4.9 × 10−10; WT versus DMSO-treated rd10, p = 7.9 × 10−9; WT versus TG6-10-1 treated rd10, p = 7.1 × 10−7; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.00024). n Photopic b-wave amplitudes from P25 CX3CR1+/GFP WT and rd10/CX3CR1+/GFP mice treated with TG6-10-1 or DMSO in response to 3 cd-s/m2 flash light intensity (F(2, 15) = 60.85, p = 6.3 × 10−8; WT versus DMSO-treated rd10, p = 2.9 × 10−7; WT versus TG6-10-1 treated rd10, p = 2.9 × 10−5; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0012). o Visual acuity was evaluated from P25 CX3CR1+/GFP WT and rd10/CX3CR1+/GFP mice treated with TG6-10-1 or DMSO (F(2, 15) = 69.48, p = 2.6 × 10−8; WT versus DMSO-treated rd10, p = 3.9 × 10−8; WT versus TG6-10-1 treated rd10, p = 1.4 × 10−5; DMSO-treated rd10 versus TG6-10-1 treated rd10, p = 0.0011). Results are presented as means ± SDs (n = 6 animals/each group). **p < 0.01 and ***p < 0.001

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