scholarly journals Metallothionein‐mediated neuroprotection of retinal ganglion cells using FLOREC retinal explants culture

2018 ◽  
Vol 96 (S261) ◽  
pp. 77-77
Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 859-868 ◽  
Author(s):  
R.C. Marcus ◽  
L.C. Wang ◽  
C.A. Mason

The visual pathway in albino animals is abnormal in that there is a smaller number of ipsilaterally projecting retinal ganglion cells. There are two possible sites of gene action that could result in such a defect. The first site is the retina where the amount of pigmentation in the retinal pigment epithelium is correlated with the degree of ipsilateral innervation (La Vail et al. (1978) J. Comp. Neurol. 182, 399–422). The second site is the optic chiasm, the site of retinal axon divergence. We investigated these two possibilities through a combination of in vivo and in vitro techniques. Our results demonstrate that the growth patterns of retinal axons and the cellular composition of the optic chiasm in albino mice are similar to those of normally pigmented mice, consistent with the albino mutation exerting its effects in the retina, and not on the cells from the chiasmatic midline. We directly tested whether the albino mutation affects the chiasm by studying ‘chimeric’ cultures of retinal explants and chiasm cells isolated from pigmented and albino mice. Crossed and uncrossed axons from pigmented or albino retinal explants display the same amount of differential growth when grown on either pigmented or albino chiasm cells, demonstrating that the albino mutation does not disrupt the signals for retinal axon divergence associated with the albino optic chiasm. Furthermore, in vitro, a greater proportion of albino retinal ganglion cells from ventrotemporal retina, origin of uncrossed axons, behave like crossed cells, suggesting that the albino mutation acts by respecifying the numbers of retinal ganglion cells that cross the chiasmatic midline.


1991 ◽  
Vol 7 (6) ◽  
pp. 513-530 ◽  
Author(s):  
Michael A. Kirby ◽  
Thomas C. Steineke

AbstractThe pattern of dendritic stratification of retinal ganglion cells in the fetal monkey (Macaca mulatta) was examined using horseradish peroxidase and retinal explants. Ganglion cells in the rhesus monkey are born between embryonic day (E) 30–70 (La Vail et al., 1983). At E60, E67, and E68, approximately 50% of all ganglion cells within the central 3.0 mm of the retina had dendritic arbors that were unistratified within the inner plexiform layer (IPL), while the remaining 50% had bistratified arbors. Unistratified cells had relatively flat arbors that ramified within a restricted portion of the IPL. In contrast, bistratified cells had one portion of the arbor that branched in the inner half of the IPL and a second portion that branched in the outer half of the IPL. Relatively few bistratified cells were encountered in the central 1.0 mm of the retina but were more numerous with increasing eccentricity. At E81, E90, and E110, the dendritic arbors of ganglion cells increased in both area and complexity, but occupied a relatively small percentage of the total depth of the IPL. The bistratified cells encountered at these fetal ages were typically located in the far retinal periphery. Between E125-E140, the dendritic arbors of individual ganglion cells increased in area and depth to occupy a greater proportion of the total IPL than at earlier fetal ages.These observations suggest that ganglion cells in the macaque undergo at least three stages of dendritic stratification: (1) an initial period of dendritic growth during which the cells have either unistratified or bistratified dendritic arbors; (2) a loss of the majority of bistratified cells through cell death or remodeling of the arbor; and (3) growth or expansion of the arbor to occupy a greater percentage of the total depth of the IPL. The first two stages are similar to recent observations in the fetal cat (Maslim & Stone, 1988) with the exception that dendritic development in the primate lacks an initial diffuse ingrowth to the IPL. Additionally, primate ganglion cells undergo a third stage of dendritic growth in late fetal development during which the arbor occupies a greater proportion of the depth of the IPL.


2021 ◽  
Author(s):  
Arianna Tolone ◽  
Wadood Haq ◽  
Alexandra Fachinger ◽  
Andreas Rentsch ◽  
Friedrich Wilhelm Herberg ◽  
...  

Hereditary retinal degeneration (RD) is often associated with excessive cGMP-signaling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can slow down the loss of photoreceptors in different RD animal models. In this study, we identified a novel PKG inhibitor, the cGMP analogue CN238, with strong protective effects on photoreceptors in retinal degeneration rd1 and rd10 mutant mice. In long-term organotypic retinal explants, CN238 preserved rd1 and rd10 photoreceptor viability and function. Surprisingly, in explanted retinae CN238 also protected retinal ganglion cells from axotomy induced retrograde degeneration and preserved their functionality. Together, these results confirm the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, thereby significantly broadening their potential applications for the treatment of retinal diseases and possibly neurodegenerative diseases in general.


Author(s):  
Kyril I. Kuznetsov ◽  
Vitaliy Yu. Maslov ◽  
Svetlana A. Fedulova ◽  
Nikolai S. Veselovsky

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