Monocular enucleation prevents retinal ganglion-cell loss following neonatal visual cortex damage in cats

1998 ◽  
Vol 15 (6) ◽  
pp. 1097-1105 ◽  
Author(s):  
KURT R. ILLIG ◽  
VON R. KING ◽  
PETER D. SPEAR
Keyword(s):  
Visual Cortex ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Cell Loss ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Medium Size ◽  
Retinal Ganglion ◽  
Retrograde Degeneration ◽  
Monocular Enucleation ◽  
Binocular Interactions

Damage to primary visual cortex (VC) in young cats leads to severe retrograde degeneration of the dorsal lateral geniculate nucleus (dLGN) and selective transneuronal retrograde degeneration of a class of retinal ganglion cells (RGCs) that have a medium-size soma. Previous studies have shown that “programmed” RGC death associated with normal development in one eye can be attenuated by removal of the other eye, suggesting that binocular interactions can influence developmental RGC death. The present study investigated whether removal of one eye also attenuates the ganglion cell loss that accompanies an early VC lesion. Five one-week-old cats received a unilateral VC lesion (areas 17, 18, and 19), and three of these cats also underwent monocular enucleation at the same time. Two normal control animals also were examined. RGC measurements were made from flat-mounted retinae when the animals were 5 weeks old. Sampling was restricted to a retinal area corresponding to the retinotopic representation included in the VC lesion. Results indicate that there is a marked loss of medium-size RGCs in the hemiretinae projecting to the damaged hemisphere in cats that received a VC lesion alone. However, there is no such loss in VC-lesion animals that also have a monocular enucleation. These results indicate that the transneuronal RGC loss that occurs after an early visual cortex lesion can be influenced by binocular interactions.

scholarly journals mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy

2020 ◽  
Author(s):  
Sanjar Batirovich Madrakhimov ◽  
Jin Young Yang ◽  
Jin Ha Kim ◽  
Jung Woo Han ◽  
Tae Kwann Park
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Retinal Ganglion ◽  
Diabetic Mice ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Apoptosis Pathway

Abstract Background: Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in diabetic retinopathy. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of diabetic retinopathy was investigated in 1-month-diabetic mice treated with phlorizin or rapamycin. The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin or MHY1485. Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis.Results: mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker – cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer (GCL), as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment. Conclusion: Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway.

Retinal ganglion cell death induced by unilateral tectal ablation in Xenopus

1989 ◽  
Vol 2 (4) ◽  
pp. 339-347 ◽  
Author(s):  
Charles Straznicky ◽  
Roger McCart ◽  
Pál Tóth
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Surgical Removal ◽  
Retinal Ganglion ◽  
Retrograde Degeneration ◽  
Optic Axons ◽  
Optic Fibers ◽  
The Right

AbstractThe survival of retinal ganglion cells (GCs) in the left eye was studied on retinal wholemounts from 2–33 weeks after the surgical removal of the right tectum in juvenile Xenopus. Two to five weeks after tectal removal, about 76% of neurons of the retinal ganglion cell (GC) layer showed signs of retrograde degeneration: swelling of their somata and chromatolysis. Neurons that were not affected by the operation were taken to be either displaced amacrine cells (DAs) or GCs not projecting to the tectum. A portion of GCs showing retrograde degeneration became pyknotic and died within the period of 2–16 weeks after operation. Counts of surviving GCs 20–33 weeks after tectal removal amounted to about 55% of the corresponding neuron number in the right intact retina of the same animal. No discernible GC loss was observed in animals where only the optic fibers were cut at their entry point to the tectum indicating that axotomy alone, followed by rapid regrowth to the target, does not adversely influence the survival of GCs. In long-surviving animals, the left optic nerve was exposed to cobaltic-lysine complex and the position of filled optic axons within the brain determined. Optic axons whose tectal target had been removed were seen to cross over to the left intact tectum via the posterior and pretectal commissures. Aberrant projections were detected to the ipsilateral tectum and the diencephalic periventricular grey in addition to an increased projection to the accessory optic nucleus. It is concluded that the removal of the tectum, the main target of optic fiber projection, induces a very substantial GC death. Since only a portion of optic fibers were able to grow to alternative targets, the surviving GCs may have also included those with main projection areas to the diencephalic visual centers.

scholarly journals Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent

2019 ◽  
Vol 286 (1897) ◽  
pp. 20182733 ◽  
Author(s):  
Colleen L. Schneider ◽  
Emily K. Prentiss ◽  
Ania Busza ◽  
Kelly Matmati ◽  
Nabil Matmati ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Visual Field ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Visual Ability ◽  
Activity Dependent

Damage to the optic radiations or primary visual cortex leads to blindness in all or part of the contralesional visual field. Such damage disconnects the retina from its downstream targets and, over time, leads to trans-synaptic retrograde degeneration of retinal ganglion cells. To date, visual ability is the only predictor of retinal ganglion cell degeneration that has been investigated after geniculostriate damage. Given prior findings that some patients have preserved visual cortex activity for stimuli presented in their blind field, we tested whether that activity explains variability in retinal ganglion cell degeneration over and above visual ability. We prospectively studied 15 patients (four females, mean age = 63.7 years) with homonymous visual field defects secondary to stroke, 10 of whom were tested within the first two months after stroke. Each patient completed automated Humphrey visual field testing, retinotopic mapping with functional magnetic resonance imaging, and spectral-domain optical coherence tomography of the macula. There was a positive relation between ganglion cell complex (GCC) thickness in the blind field and early visual cortex activity for stimuli presented in the blind field. Furthermore, residual visual cortex activity for stimuli presented in the blind field soon after the stroke predicted the degree of retinal GCC thinning six months later. These findings indicate that retinal ganglion cell survival after ischaemic damage to the geniculostriate pathway is activity dependent.

scholarly journals Article Commentary: Retinal Ganglion Cell Loss in Diabetes Associated with Elevated Homocysteine

2009 ◽  
Vol 1 ◽  
pp. OED.S3417 ◽  
Author(s):  
Kenneth S. Shindler
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cell Layer ◽  
Ganglion Cells ◽  
Cell Layer ◽  
Cell Loss ◽  
Diabetic Patients ◽  
Retinal Ganglion ◽  
Heterozygous Deletion ◽  
Retinal Pathology

A number of studies have suggested that homocysteine may be a contributing factor to development of retinopathy in diabetic patients based on observed correlations between elevated homocysteine levels and the presence of retinopathy. The significance of such a correlation remains to be determined, and potential mechanisms by which homocysteine might induce retinopathy have not been well characterized. Ganapathy and colleagues 1 used mutant mice that have endogenously elevated homocysteine levels due to heterozygous deletion of the cystathionine-β-synthase gene to examine changes in retinal pathology following induction of diabetes. Their finding that elevated homocysteine levels hastens loss of cells in the retinal ganglion cell layer suggests that toxicity to ganglion cells may warrant further investigation as a potential mechanism of homocysteine enhanced susceptibility to diabetic retinopathy.

The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss

2017 ◽  
Vol 164 ◽  
pp. 37-45 ◽  
Author(s):  
Román Blanco ◽  
Gema Martínez-Navarrete ◽  
Francisco J. Valiente-Soriano ◽  
Marcelino Avilés-Trigueros ◽  
Consuelo Pérez-Rico ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Cell Loss ◽  
Retinal Ganglion ◽  
Endothelin 1 ◽  
S1p1 Receptor ◽  
Selective Agonist

scholarly journals mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy

2020 ◽  
Author(s):  
Sanjar Batirovich Madrakhimov ◽  
Jin Young Yang ◽  
Jin Ha Kim ◽  
Jung Woo Han ◽  
Tae Kwann Park
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Retinal Ganglion ◽  
Diabetic Mice ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Subcutaneous Injections

Abstract Background: Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in diabetic retinopathy. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of diabetic retinopathy was investigated in 1-month-diabetic mice treated with phlorizin (two daily subcutaneous injections at a dose of 200 mg/kg of body weight during the last 7 full days of the experiment and the morning of the 8th day, 3 h before sacrifice) or rapamycin (daily intraperitoneal injections, at a dose of 3mg/kg for the same period as for phlorizin treatment). The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin (two daily subcutaneous injections during the last 10 full days of the experiment and the morning of the 11th day, 3 h before sacrifice) or MHY1485 (daily i.p. injections, at a dose of 10 mg/kg for the same period as for phlorizin treatment). Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis.Results: mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker – cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer (GCL), as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment. Conclusion: Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway.

Prenatal disruption of binocular interactions creates novel lamination in the cat's lateral geniculate nucleus

1988 ◽  
Vol 1 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Preston E. Garraghty ◽  
Carla J. Shatz ◽  
Mriganka Sur
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Lateral Geniculate Nucleus ◽  
Retinal Ganglion ◽  
Monocular Enucleation ◽  
Lateral Geniculate ◽  
Binocular Interactions ◽  
Soma Size ◽  
Cell Layers ◽  
Normal Nucleus

AbstractThe elimination of retinogeniculate afferents from one eye on embryonic day 44 (E44) has pronounced effects on the formation of the cellular laminae in the cat lateral geniculate nucleus (LGN). Only two laminae form: a dorsal, “magnocellular” layer, and a ventral, “parvocellular” layer. Soma size measurements and previously reported patterns of termination of retinogeniculate axons suggest that the dorsal lamina is a coalescence of the normal A-laminae and the dorsal, magnocellular division of layer C, while the ventral layer is a composite of the parvocellular sublamina of layer C and the remaining C-laminae. This is a novel pattern of lamination in the LGN that differs from that found in the normal nucleus, not only in that there are now only two cell layers rather than the normal five, but also in that the interlaminar zone occurs in an abnormal location. This result is markedly different from that observed in other species where interlaminar zones present after early monocular enucleation are a subset of the ones which would normally be present. We suggest that, in the absence of ongoing binocular interactions, interactions between functionally distinct retinal ganglion cell classes from the remaining eye may direct the formation of cell laminae in the LGN, even when such interactions are not normally operative.

Transneuronal degeneration of beta retinal ganglion cells in the cat

1984 ◽  
Vol 222 (1226) ◽  
pp. 15-32 ◽  
Keyword(s):  
Visual Cortex ◽  
Retinal Ganglion Cells ◽  
Lateral Geniculate Nucleus ◽  
Ganglion Cells ◽  
Dendritic Morphology ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Retinal Ganglion ◽  
Normal Numbers ◽  
Lateral Geniculate ◽  
Dorsal Lateral Geniculate

Transneuronal retrograde degeneration of retinal ganglion cells was investigated following neonatal visual cortex ablation in the cat. After a survival time of at least 18 months, retinal ganglion cells projecting to the thalamus were labelled by retrograde transport of horseradish peroxidase. Filled ganglion cells were classified into α , β and γ types on the basis of dendritic morphology. In normal cats, α cells made up 8-10% of the total population in the sample area, β cells made up 64-67% and γ cells made up 23-27%. In retinae of visual cortex-ablated cats, normal numbers of α and γ cells were present, but the β cell population was depleted by 90% of normal. Thalamic projections of surviving retinal ganglion cells were investigated by anterograde transport of tritiated proline injected into the eye. In these animals, ablation of visual cortex resulted in almost complete degeneration of laminae A and A1 of the dorsal lateral geniculate nucleus. In the radioautographic material, projections from the retina to the degenerated parts of laminae A and A1 were barely detectable. Survival of some ganglion cell populations and death of others after neonatal visual cortex ablation may be explained in terms of the pattern of projections of the different cell types. We conclude that the majority of β cells degenerate following visual cortex ablation because of removal of cells in the dorsal lateral geniculate nucleus which form their sole or principal target. Alpha and γ cells and 10% of β -cells survive because of extensive collateral projections to targets other than cells of the laminae A and A1 of dorsal lateral geniculate nucleus.

scholarly journals mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sanjar Batirovich Madrakhimov ◽  
Jin Young Yang ◽  
Jin Ha Kim ◽  
Jung Woo Han ◽  
Tae Kwann Park
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Retinal Ganglion ◽  
Diabetic Mice ◽  
Tissue Samples ◽  
Glucose Transporter 1 ◽  
Subcutaneous Injections

Abstract Background Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in DR. Methods Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of DR was investigated in 1-month-diabetic mice treated with phlorizin (two daily subcutaneous injections at a dose of 200 mg/kg of body weight during the last 7 full days of the experiment and the morning of the 8th day, 3 h before sacrifice) or rapamycin (daily intraperitoneal injections, at a dose of 3 mg/kg for the same period as for phlorizin treatment). The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin (two daily subcutaneous injections during the last 10 full days of the experiment and the morning of the 11th day, 3 h before sacrifice) or MHY1485 (daily i.p. injections, at a dose of 10 mg/kg for the same period as for phlorizin treatment). Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis. Results mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker—cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer, as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment. Conclusion Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway.

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