Biomedical subjects

S F Geller

Publications and source records attributed to S F Geller.

6 recordsLinked to original sources

PubMed2001

FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells.

PURPOSE: To identify changes in cellular signaling pathways and AP-1 expression in retina and retinal pigmented epithelium (RPE) after experimental retinal detachment (RD). METHODS: Cat and rabbit neural retinas were separated from the RPE in vivo for 5 minutes to 28 days. Tissues were removed and processed for Western blotting, immunohistochemistry, in situ hybridization, and immunoprecipitation experiments. RESULTS: An ordered sequence of events occurs after RD: (1) fibroblast growth factor (FGF) receptor 1 (FGFR1, flg) is phosphorylated in the retina within 15 minutes and dephosphorylated 2 hours after RD; (2) The extracellular signal-regulated kinase (ERK) is phosphorylated in both Müller and RPE cells within 15 minutes and remains so for several days; (3) De novo expression of c-fos mRNA coincides with increased c-Fos and c-Jun immunoreactivity in both Müller and RPE cells; (4) CREB is phosphorylated in a subpopulation of photoreceptors; and (5) STAT3 and NF-kappaB are activated in inner nuclear layer cells by 1 day of RD. CONCLUSIONS: These data suggest that nonneuronal cells (RPE and Müller cells) respond to RD very rapidly by stimulating ERK signaling and AP-1 transcription factor expression. Furthermore, these data suggest that basic fibroblast growth factor (FGF-2, bFGF) is involved in initiating the retina's earliest responses to RD. The events described here precede changes in gene expression and morphology that can have serious effects on visual outcome in humans treated for retinal detachment or other retinal injuries.

Animals↗

PubMed1999

Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment.

PURPOSE: To examine the effects of brain-derived neurotrophic factor (BDNF) in an animal model of retinal detachment. METHODS: Cat retinas were detached from the retinal pigment epithelium for either 7 or 28 days. Animals received either an intravitreal injection of BDNF (100 ILg) or phosphate-buffered saline (PBS), the vehicle for BDNF. Retinas were evaluated using morphology and immunocytochemistry. The width of the outer segment zone was measured, and the retinas were evaluated for changes in protein expression by labeling with antibodies to rod opsin, phosducin, synaptophysin, calbindin D, and glial fibrillary acidic protein (GFAP). The effect of BDNF on both proliferation and apoptotic cell death was examined. RESULTS: Although there was variability in the treated retinas, most of the animals receiving BDNF had well-organized outer segments that were longer than those in vehicle-treated controls. Immunocytochemistry revealed that treated retinas had consistently less opsin redistribution to the plasma membrane, less phosducin upregulation, and fewer calbindin D-labeled horizontal cell processes. BDNF did not reduce overall cell death in the detachments or death of photoreceptors by apoptosis. However, it significantly reduced the proliferative response of Miller cells and the extent of upregulation of GFAP. CONCLUSIONS. The results suggest that BDNF may aid in the recovery of the retina after reattachment by maintaining the surviving photoreceptor cells, by reducing the gliotic effects in Müller cells, and perhaps by promoting outer segment regeneration.

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PubMed1998

Distribution, size and number of axons in the optic pathway of ground squirrels.

The present study has examined the distribution of axons of differing sizes in the optic pathway of the ground squirrel. Axon diameters were measured from electron micrographs at various locations across sections of the optic nerve and tract, and total distributions and numbers were estimated. In both the nerve and tract, roughly 1.2 million optic axons were present. The population of optic axons had a unimodal size distribution, peaking at 0.9 microm in diameter and having an extended tail toward larger diameters. Local axon diameter distributions in the optic tract indicated distinct (though partially overlapping) axon diameter classes, including one of fine sizes peaking at 0.8-0.9 microm, a second of medium sizes peaking around 1.7-1.8 microm, and a third composed of the larger fibers with diameters up to 4.8 microm. The fine-caliber axons were found at all locations in the tract, and were the only axons present immediately adjacent to the pia, while the medium- and coarse-caliber axons were found at deeper locations. Curiously, the larger axons were found primarily in the medial parts of the tract, where axons from the dorsal retina normally course. A similarly restricted distribution of the larger axons was observed in the dorsotemporal parts of the optic nerve, suggesting that this difference in the tract may relate to an asymmetric distribution of ganglion cells on the retina giving rise to these axons. Measurements of axonal size taken within the optic fiber layer in dorsal and ventral parts of the retina confirmed this asymmetry, consistent with previous demonstrations of soma size differences in the dorsal versus ventral retina. The partial segregation of axons by size in the optic tract of the ground squirrel then reflects both the asymmetric distribution of retinal ganglion cell classes and the chronotopic reordering of optic axons that occurs within the chiasmatic region.

Animals↗

PubMed1997

Cellular retinaldehyde binding protein in developing retinal astrocytes.

Cellular retinaldehyde binding protein (CRALBP) is present in Müller glia and in cells of the retinal pigment epithelium, but we have recently observed CRALBP-like immunoreactivity near the inner limiting membrane in the newborn mouse retina. The present study has examined whether this protein is present in developing retinal astrocytes. Retinal tissue was collected at various embryonic and postnatal ages and in adulthood. Tissue for immunohistochemistry was fixed by immersion in 4% paraformaldehyde and immunostained using rabbit polyclonal antisera to CRALBP or glial fibrillary acidic protein (GFAP), while fresh tissue was homogenized for Western analysis. Specificity of the antiserum for the 33 kDa protein was shown in retinal homogenates by immunoblotting, with expression of the protein increasing steadily from E15.5 through adulthood. Immunostaining of sections from fetal eye-cups revealed faint labeling of cells in the optic nerve, with progressive migration of CRALBP-immunoreactive cells into the retina at the inner limiting membrane during the perinatal period. By the day of birth, these cells were intensely immunoreactive, showing a morphology characteristic of migrating astrocytes. These CRALBP-immunoreactive cells mimicked the progressive infiltration of GFAP-positive astrocytes which are known to migrate into the retina from the optic nerve head, many of which were double-labeled with GFAP. Their distribution across the retina is distinct from that of the lighter-staining Müller glial somata during these stages, and they are not misidentified Müller glial endfeet. Astrocytes are only transiently CRALBP-immunoreactive, no longer containing the protein after the second post-natal week. Preincubation of the antiserum with purified CRALBP abolished all staining of astrocytes. Coupled with the fact that only a single (approximately 33 kDa) molecular weight protein is labeled by the antiserum, it was concluded that retinal astrocytes contain CRALBP during a limited period of development.

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PubMed1995

Precocious invasion of the optic stalk by transient retinopetal axons.

This study demonstrates that the fetal optic nerve contains a conspicuous population of transient retinopetal axons. Implants of the carbocyanine dye, DiI, were made into the retina or diencephalon of fetal ferrets to label the retinopetal axons retrogradely or anterogradely, respectively, and sections were immunostained for beta-tubulin to label the early differentiating axons in the optic nerve. Dye implants into the optic nerve head, but not the retinal periphery, retrogradely labeled somata in the ventrolateral diencephalon, provided the implants were made before embryonic day (E) 30. When dye implants were made into the ventrolateral diencephalon, these same retinopetal axons were anterogradely labeled, coursing through the optic nerve but never invading the retina. The axons course as 2-5 fascicles from their cells of origin and turn laterally to enter the optic nerve where it joins the future hypothalamus. The retinopetal cells can be retrogradely labeled as early as E20, before optic axons have left the retina. The optic nerve and fiber layer are immunoreactive for beta-tubulin on E24 and thereafter, whereas on E20 and E22, they are immunonegative. Yet at these early embryonic ages, immunopositive fascicles of axons course from the diencephalon into the optic stalk, confirming the precocious nature of the retinopetal projection. Implants of dye made into the future optic nerve head at these very early stages also retrogradely label retinopetal cells in the future chiasmatic region. These cells are distributed primarily on the side ipsilateral to the midline, but a few can be found contralateral to it. Both these, as well as the retinopetal axons arising from the ventrolateral diencephalon, may serve a transient guidance function for later developing optic axons.

Afferent Pathways↗

PubMed1995

Use of the MIB-1 antibody for detecting proliferating cells in the retina.

PURPOSE: To study intraretinal proliferation as a response to experimental retinal detachment using an antibody that recognizes the nuclear specific antigen Ki-67 in proliferating cells. METHODS: Experimental retinal detachments were produced in cats (1, 3, 7, and 28 days) and rabbits (1, 3, and 7 days). The animals were killed and the eyes were fixed and embedded in paraffin. Histologic sections were processed for immunohistochemistry using the MIB-1 antibody to detect the Ki-67 protein. Labeled cells were identified, and the proliferative response was quantified. RESULTS: In normal cat retina, approximately 0.05 cells per millimeter of retina are labeled. In cat retina detached for 1, 3, 7, or 28 days, the number of cells labeled by MIB-1 is 0.06, 5.03, 1.38, and 0.23 cells per millimeter of retina, respectively. MIB-1 labeling yields an approximate fivefold increase over the number of proliferating cells detected in retinal sections using 3H-thymidine autoradiography. Detachment of the rabbit retina elicits a similar response as measured by MIB-1 immunohistochemistry. CONCLUSIONS: In contrast to 3H-thymidine, which labels cells in S-phase only, the MIB-1 antibody labels proliferating cells regardless of their location within the cell cycle. MIB-1 labeling, therefore, is a more accurate means of evaluating cellular proliferation in the retina and elsewhere in the central nervous system, and it is a relatively simple way of evaluating the effects of agents that may affect this response.

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