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Biomedical subjects

J A Sahel

Publications and source records attributed to J A Sahel.

14 recordsLinked to original sources
PubMed1998

Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse.

The role of cellular interactions in the mechanism of secondary cone photoreceptor degeneration in inherited retinal degenerations in which the mutation specifically affects rod photoreceptors was studied. We developed an organ culture model of whole retinas from 5-week-old mice carrying the retinal degeneration mutation, which at this age contain few remaining rods and numerous surviving cones cocultured with primary cultures of mixed cells from postnatal day 8 normal-sighted mice (C57BL/6) retinas or retinal explants from normal (C57BL/6) or dystrophic (C3H/He) 5-week-old mice. After 7 days, the numbers of residual cone photoreceptors were quantified after specific peanut lectin or anti-arrestin antibody labeling by using an unbiased stereological approach. Examination of organ cultured retinas revealed significantly greater numbers of surviving cones (15-20%) if cultured in the presence of retinas containing normal rods as compared with controls or cocultures with rod-deprived retinas. These data indicate the existence of a diffusible trophic factor released from retinas containing rod cells and acting on retinas in which only cones are present. Because cones are responsible for high acuity and color vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to define interactions between retinal photoreceptor types.

Animals↗
PubMed1997

Intravitreal injection of ganglioside GM1 after ischemia reduces retinal damage in rats.

BACKGROUND AND PURPOSE: Gangliosides are normal components of cell membranes and contribute to structural rigidity and membrane function. They have been shown to protect against various insults in the brain. We have shown previously that GM1 administered intraperitoneally before the induction of retinal ischemia provides a protective effect. This study evaluates the protective effect of GM1 administered intravitreally after ischemia on retinal lesions. METHODS: We induced retinal ischemia unilaterally in Long-Evans rats by increasing intraocular pressure to 160 mm Hg for 60 minutes. GM1 (20 microL x 10(-5) mol/L) or saline (20 microL) was injected into the vitreous 15 minutes after ischemia, and the postischemic survival time was either 8 or 15 days. The degree of retinal damage was assessed by histopathological study. RESULTS: Retinal ischemia led to reductions in thickness and cell number, principally in the inner retinal layers (39% to 80%) and to a lesser extent in the outer retinal layers (26% to 45%). Postischemic treatment with intravitreally injected GM1 conferred significant protection against retinal ischemic damage after both 8 and 15 days of survival time. After 8 days of reperfusion, the ischemia-induced loss in overall retinal thickness was reduced by 15% and those of the inner nuclear and plexiform layers by 44% and 17%, respectively. Ischemic-induced ganglion cell and inner nuclear cell density losses were reduced by 37% and 27%, respectively. After 15 days of reperfusion, approximately the same statistically significant differences could be observed in comparison with the 15-day saline-injected group. CONCLUSIONS: GM1 protects the rat retina from pressure-induced ischemic injury when given intravitreally after the insult. The protection provided by GM1 after initiation of retinal damage could be of therapeutic interest.

Animals↗
PubMed1996

Monosialoganglioside GM1 reduces ischemia--reperfusion-induced injury in the rat retina.

PURPOSE: Gangliosides are normal components of cell membranes, contribute to structural rigidity and membrane function, and have been shown to protect against various insults to the brain. This study evaluates the effect of exogenously administered monosialoganglioside GM1 on retinal damage induced by transient retinal ischemia and reperfusion. METHODS: Retinal ischemia was induced unilaterally in Long Evans rats by increasing intraocular pressure to 160 mm Hg for 60 minutes. GM1 (30 mg/kg, intraperitoneally) or buffer controls were administered at 48 hours, and 15 minutes before ischemia, and survival time after ischemia was either 8 or 15 days. The degree of retinal damage was assessed by histopathologic study according to Hughes' quantification of ischemic damage. RESULTS: Retinal ischemia led to significant reductions in thickness and cell number, principally in the inner retinal layers (30% to 80%), and to a lesser extent in the outer retinal layers (18% to 42%). Pretreatment with intraperitoneally injected monosialoganglioside GM1 conferred significant protection against retinal ischemic damage either 8 or 15 days after ischemic survival time. After 8 days reperfusion, the ischemic-induced loss in overall retinal thickness was reduced by 70%, and those of the inner nuclear and plexiform layers were reduced by 77% and 44%, respectively. Ischemic-induced ganglion cell, inner nuclear, and outer nuclear layer cell density losses were reduced by 45%, 40%, and 57%, respectively. After 15 days of reperfusion, approximately the same statistically significant differences could be observed in comparison with the 15-day ischemic--reperfusion group. CONCLUSIONS: Monosialoganglioside GM1 protects the rat retina from pressure-induced ischemic injury when administered intraperitoneally 2 days before insult. This protection afforded by GM1 can be observed even after 8 days or 15 days of reperfusion.

Animals↗
PubMed1996

[Retinal grafts: biological problems and clinical stakes].

Retinal transplantation, formerly perceived as unrealistic, has become over the past decade a major clinical and biological undertaking in several laboratories and eye clinics. We describe the insights gained through the pioneering experimental works of Del Cerro et al, Turner et al, Gouras et al, Aramant et al, Lund et al e.g. the survival of transplants, the lack of immune response to photoreceptors, their integration and expression of neuronal markers, but also the dysplastic arrangement into rosettes and the lack of a definitive proof for functionality. Our laboratory has undertaken to establish the trophic and synaptic functions of sheets of photoreceptors transplanted, as described by Silverman et al, in the subretinal space of mutant rd mice carrying a retinal degeneration similar to human retinitis pigmentosa. Clinical applications to this condition as well as in cases of end-stage age related macular degeneration are discussed.

Animals↗
PubMed1996

[Iodine 125 curietherapy of choroidal melanomas. Values of the technique and initial results].

PURPOSE: Among conservative treatment of the choroidal melanoma, improved functional capacities can be provided with Iodine 125 and with a treatment planning system for optimized dosimetry. METHODS: Forty patients were treated with Iodine 125 with a minimal follow-up period of 6 months and a mean follow up of 25 months. RESULTS: Response to the treatment based on tumor regression or stabilization was 97%. Complication rate was 32%. Retinopathy was the major cause of loss of vision and was linked to the proximity of the tumor to the macula. Two patients developed metastasis and one required enucleation for tumor regrowth. CONCLUSION: Brachytherapy with Iodine 125 was found to be effective on tumor growth within the limits of the follow-up. High doses (100 Gy) given to the apex of the tumor did not increase complications rate. Many years will be necessary to assess efficiency of such a procedure in terms of preventing complications.

Adult↗
PubMed1995

Protective role of excitatory amino acid antagonists in experimental retinal ischemia.

BACKGROUND: Excitatory amino acids and their analogues (NMDA, kainate and AMPA) are implicated in the pathogenesis of ischemic brain injury. In order to fully understand their involvement in the pathogenesis of retinal ischemic injury, we studied the electrophysiological and histopathological effects of two excitatory amino acid antagonists, cis-PDA and MK 801, in an experimental retinal ischemia model. METHODS: The two antagonists were injected intravitreously 15 min before ischemia was induced by elevatory intraocular pressure caused by external compression. Electrophysiological and histopathological evaluation was made 48 h after 45 min transient ischemia. RESULTS: The excitatory amino acid antagonists cis-PDA and MK 801 can partially protect against retinal ischemic injury; whereas the mean post-ischemic b-wave amplitude corresponded to 41% of the pre-ischemic value in the control group, it was 64% (P = 0.003) and 59% (P = 0.005) following administration of cis-PDA and MK 801 respectively. Histopathological study corroborated these data, showing significant differences for morphometric parameters (P = 0.011 and P = 0.007 respectively). CONCLUSION: These preliminary results suggest the possibility of limiting excito-toxicity, one of the lesion-forming mechanisms in ischemic retinal injury.

Animals↗
PubMed1991

Mitogenic effects of excitatory amino acids in the adult rat retina.

We studied the retinas of adult rats after the intravitreal injection of excitatory amino acids and ouabain. Kainic acid, domoic acid, N-methyl D-asparate and ouabain produced swelling and vacuolization of the outer plexiform, inner nuclear and inner plexiform layers and pyknosis. Mitoses were present in retinas treated with all agents other than N-methyl D-asparate. Rompun ketamine anesthesia blocked the mitogenic effects. Immunohistochemical labeling of both glial fibrillary acidic protein and S100 protein would indicate that the mitoses are occurring in glial cells. We suggest that the mitogenic effects are mediated through action on glial cationic channels, and might account for the reactive gliosis observed in some retinal lesions.

Animals↗
PubMed1989

Malignant transformation of an iris melanocytoma. A case report.

A 34-year-old Caucasian woman was diagnosed as having a pigmented iris tumor showing recent growth and satellite lesions. The tumor was associated with pigmentation of the anterior chamber angle and secondary unilateral glaucoma. After local excision, histopathologic studies revealed the plump polyhedral cells typical of melanocytoma. However, the examination of additional sections showed evidence of malignancy. The diagnosis of a melanocytoma that transformed into malignant melanoma was made and later confirmed by electron microscopic studies. Following surgical excision of the tumor, the eye maintained normal intraocular pressure. There was no evidence of recurrence 4 years after surgery.

Adult↗
PubMed1989

Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia.

A 67-year-old man presented with a diffuse choroidal and ciliary body infiltrate, suggesting clinically and ultrasonographically a diffuse uveal melanoma. After enucleation both morphological and immunohistochemical data were highly suggestive of a diffuse, low-grade B cell lymphoma or lymphoplasmacytic immunocytoma. The difficulties of clinical and histopathological differential diagnosis of uveal lymphoid infiltrates are emphasised. In view of the excellent life prognosis of these tumours, treatment of the patient should be directed towards the preservation of ocular function.

Aged↗
PubMed1988

Melanoma arising de novo over a 16-month period.

Choroidal melanoma is widely regarded as a slow-growing tumor. We report herein the first documented case, to our knowledge, of a choroidal melanoma present in an eye in which examination 16 months earlier disclosed no tumor. On gross examination following enucleation, the largest tumor diameter at the base was 19 mm and the height was 11 mm. The implications as to the growth rate and the precursor lesions of choroidal melanomas are discussed.

Aged↗
PubMed1988

Idiopathic retinal gliosis mimicking a choroidal melanoma.

A 37-year-old woman has followed for more than 10 years with an amelanotic peripheral intraocular tumor. This solitary lesion grew slowly and, because of the possibility of an amelanotic melanoma, the eye was enucleated. Histopathology revealed a localized "massive" retinal gliosis (MRG). Immunohistochemical staining for S-100 protein and glial fibrillary acidic protein (GFAP) were positive. Electron microscopy showed a highly fibrillar component and basement membrane formation in the extracellular space. Proliferating cells contained abundant fine filaments. These findings confirmed the glial origin of the proliferating cells. The previously undefined relationship of these localized forms of MRG with solitary astrocytomas is discussed.

Adult↗
PubMedDate not supplied

[Poisoning of retinal pigment epithelium by deferoxamine. A case report].

A patient undergoing hemodialysis was treated intravenously with desferrioxamine (3 g) for an aluminum encephalopathy. He presented a sudden xanthopsia with visual loss. Fundus examination showed diffuse macular irregular pigmentary disturbances. We discuss current knowledge and possible pathogenesis of these observations published since 1983. Awareness of the side effects of desferrioxamine implies an ophthalmologic follow up similar as chloroquine.

Aged↗
PubMedDate not supplied

[Proliferation of retinal glia and excitatory amino acids].

Kainic acid administered intravitreally induced mitogenic effects in the adult rat retina at doses ranging from 60 nm to 200 nm. Similar effects resulted from the injection of domoic acid at doses ranging from 20 nm to 400 nm, and ouabain. L-glutamate, N-methyl D-aspartate and quisqualate provoked similar cytotoxic effects, i.e., swelling and vasuolization of the outer plexiform, inner nuclear and inner plexiform layer, and cell pycnosis. The latter induced no mitoses. The use of Rompun ketamine as anesthetic blocked the mitogenic effects. The immunohistochemical labelling of both glial fibrillary acidic protein and S100 protein in the dividing cells and the location of dividing nuclei in the inner nuclear layer are arguments for their Müllerian nature. We suggest that the mitogenic effects could account for reactive gliosis observed in some clinical conditions.

Amino Acids↗