Hematopoietically derived retinal perivascular microglia initiate uveoretinitis in experimental autoimmune uveitis.

BACKGROUND: Hematopoietically derived cells in the retina were studied for the expression of molecules associated with antigen presentation. METHODS: Bone marrow cells of (Lewis x Brown Norway) F1 rats (LBNF1) were transplanted to sublethally irradiated Brown Norway (BN) rats to construct chimeric rats (LBNF-->BN). Each of 21 established chimeras received an adoptive transfer of uveitogenic Lewis T lymphocytes. Three rats were killed on each of 7 consecutive days. The right eye of each rat was processed for flat-mount preparation of the retina; the left eye of each was frozen for cryostat sectioning. All tissues were then stained with one of the following antibodies: OX-3 (Lewis-specific MHC class II marker), anti-ICAM, anti-B7- 1, anti-TNF-alpha or anti-IL-1beta. RESULTS: Initial clinical signs of EAU appeared first on day 4; by day 6, full-blown EAU was noted. The flatmount preparations revealed the presence of OX-3+ cells in the retina, perivascularly exhibiting dendritic morphology on day 2. These cells were observed in the retinal nerve fiber layer (NFL). No B7-1+, ICAM-1+, TNF-alpha+ or IL-1beta + cells were detected. Cryostat sections revealed positive cell staining of perivascular microglia and astrocytes in the retinal NFL with anti-IL-1beta and anti-TNF-alpha antibodies. CONCLUSIONS: Since only perivascular bone marrow-derived cells are seen to express MHC class II molecules prior to onset of EAU, and since these cells also generate the cytokines IL- 1beta and TNF-alpha, it appears that initial presentation of antigen in the retina could be by these cells.

The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study.

The purpose of this study was to determine the long-term safety of transplanting human fetal neuroretinal cells (14 to 18 week gestational age) into a series of patients with advanced retinitis pigmentosa (RP). After obtaining informed consent, both hosts and mothers of donors were screened for transmissible diseases. Pre- and postoperative clinical exams, visual acuity, electroretinograms, and fluorescein angiograms were performed and visual field testing was attempted in each case. Surgically, an anterior approach through pars plana ciliaris was used. A retinotomy was performed in the paramacular area and a two-function cannula was introduced into the subretinal space to deliver a suspension of donor cells. The cell suspension carried approximately 4000 cells/microl; the volume injected did not exceed 150 microl. The patients were examined for periods ranging from 12 to 40 months posttransplantation. To date, no evidence of inflammation, infection, or overt rejection of the graft was noted in the host eye, neither was any change observed in the contralateral, unoperated eye. In conclusion, neuroretinal cells were injected into the subretinal space of 14 patients with advanced RP with no clinical appearance of detrimental effects at the time of surgery or up to 40 months postinjection except in 1 patient who developed retinal detachment. This sets the stage for a phase II clinical trial to determine the possible beneficial effects of this procedure in patients blinded by degenerative retinal disease.

Antigen-presenting cells in experimental autoimmune uveoretinitis.

The present study attempts to identify the antigen-presenting cells in the retina, utilizing bone marrow-transplanted chimeric rats. Two types of chimeras were used: one produced by transplanting bone marrow cells from F1 hybrids of Lewis and Brown Norway (BN) into sublethally irradiated Brown Norway rats (LBN/F1-->BN), followed by adoptive transfer of S-antigen-specific T cells obtained from Lewis rats; the second produced by transplanting bone marrow cells from BN rats into sublethally irradiated F1 hybrids (BN-->LBN/F1), followed by adoptive transfer of S-antigen-specific T cells obtained from F1 hybrids. As controls, Lewis, F1 hybrids and BN rats also received adoptive transfer of syngeneic uveitogenic T cell lines. All animals were killed on the seventh day after adoptive transfer and their eyes and pineal glands were analysed immunohistochemically, utilizing antibody directed against Lewis specific MHC class II molecules(OX-3). The analyses revealed the development of uveoretinitis and pinealitis in both types of chimeras and in the Lewis and F1 hybrid rats. BN rats did not develop uveoretinitis. OX-3-positive cells were found in the retina and the pineal glands of both types of chimeras, and in the Lewis and F1 hybrid rats but not in the BN rats. These cells in the retina expressed dendritic morphology and perivascular distribution. Retinal pigment epithelia, Müller cells and the vascular endothelia of both chimeras, the two strains, and the F1 hybrid rats did not demonstrate OX-3-positive staining. These results suggest that the bone marrow-derived cells in the retina and pineal gland may present S-antigen to T cells, initiating the cascade of uveoretinitis and pinealitis.

Visual Information and Object Size in the Control of Reaching.

The role of vision in the control of reaching and grasping was investigated by varying the available visual information. Adults (N = 7) reached in conditions that had full visual information, visual information about the target object but not the hand or surrounding environment, and no visual information. Four different object diameters were used. The results indicated that as visual information and object size decreased, subjects used longer movement times, had slower speeds, and more asymmetrical hand-speed profiles. Subjects matched grasp aperture to object diameter, but overcompensated with larger grasp apertures when visual information was reduced. Subjects also qualitatively differed in reach kinematics when challenged with reduced visual information or smaller object size. These results emphasize the importance of vision of the target in reaching and show that subjects do not simply scale a command template with task difficulty.

Colour of the nucleus as a marker of nuclear hardness, diameter and central thickness.

Hundred and thirty patients, aged above 40 years, with senile cataract were examined. Age and colour were selected as the probable preoperative indicators of nuclear hardness. The lens material collected after manual extracapsular extraction was washed and the nucleus isolated. The diameter and central thickness of the nucleus were measured; the mean diameter and mean central thickness were 7.13 mm +/- 0.76 and 3.05 mm +/- 0.48, respectively. The hardness of the nucleus was measured with a lens guillotine designed by us. Regression analysis was applied to the parameters measured and these were compared with the colour and age. The parameters measured had the following relationship: Colour vs hardness (r value = 0.7569) (p < 0.001) Colour vs diameter (r value = 0.3962) (p < 0.001) Colour vs central thickness (r value = 0.4785) (p < 0.001) Age vs hardness (r value = -0.0499) (p > 0.05) Age vs diameter (r value = 0.0987) (p > 0.05) Age vs central thickness (r value = 0.1700) (p > 0.05) The values showed that colour had a statistically significant relationship with all the 3 parameters (p < 0.001), while age had no significant relationship with the same parameters. The results indicated that colour can be used more reliably to predict physical characteristics of the cataractous lens nucleus, the preoperative knowledge of which would help the surgeon in planning small-incision surgery including phacoemulsification.