Edward Hughes

Neural progenitor cells from postmortem adult human retina

Background: Given the presence of neural progenitor cells (NPC) in the retina of other species capable of differentiating into multiple neural components, the authors report the presence of NPC in the adult human retina. A resident population of NPC suggests that the retina may constitutively replace neurons, photoreceptors, and glia. Methods: Adult human postmortem retinal explants and cell suspensions were used to generate cells in tissue culture that display the features of NPC. The phenotype of cells and differentiation into neurons was determined by immunocytochemistry. Dividing cells were labelled with 5-bromo-2-deoxyuridine (BrdU) and neurospheres were generated and passaged. Results: Cells labelled with nestin, neurofilament M (NFM), rhodopsin, or glial fibrillary acidic protein (GFAP) grew out from explant cultures. BrdU labelling of these cells occurred only with basic fibroblast growth factor (FGF-2). Dissociated retina and pars plana generated primary neurospheres. From primary neurospheres, NPC were passaged to generate secondary neurospheres, neurons, photoreceptors, and glia. BrdU labelling identified dividing cells from neurospheres that differentiated to express NFM and rhodopsin. Conclusion: The adult human retina contains NPC and may have the potential to replace neurons and photoreceptors. This has implications for the pathogenesis and treatment of retinal disorders and degenerations, including glaucoma, and those disorders associated with retinal scarring.

Control of myeloid activity during retinal inflammation

Combating myeloid cell‐mediated destruction of the retina during inflammation or neurodegeneration is dependent on the integrity of homeostatic mechanisms within the tissue that may suppress T cell activation and their subsequent cytokine responses, modulate infiltrating macrophage activation, and facilitate healthy tissue repair. Success is dependent on response of the resident myeloid‐cell populations [microglia (MG)] to activation signals, commonly cytokines, and the control of infiltrating macrophage activation during inflammation, both of which appear highly programmed in normal and inflamed retina. The evidence that tissue CD200 constitutively provides down‐regulatory signals to myeloid‐derived cells via cognate CD200‐CD200 receptor (R) interaction supports inherent tissue control of myeloid cell activation. In the retina, there is extensive neuronal and endothelial expression of CD200. Retinal MG in CD200 knockout mice display normal morphology but unlike the wild‐type mice, are present in increased numbers and express nitric oxide synthase 2, a macrophage activation marker, inferring that loss of CD200 or absent CD200R ligation results in “classical” activation of myeloid cells. Thus, when mice lack CD200, they show increased susceptibility to and accelerated onset of tissue‐specific autoimmunity.

The pathology and pathogenesis of retinal vasculitis.

Retinal vasculitis is a rare, but potentially blinding intraocular inflammatory condition with diverse aetiology. Although commonly idiopathic, it has a strong association with systemic inflammatory diseases known to involve other areas of the central nervous system, most notably Behcets disease, sarcoidosis, systemic lupus erythematosis and multiple sclerosis. This article describes the clinicopathologic features of retinal vasculitis and its visually damaging sequelae, reviewing available human histopathologic studies and work with experimental models to discuss the pathogenesis and immunopathology. Evidence indicates that noninfective retinal vasculitis is an autoimmune condition that may be induced by antecedent infection with microbes cross–reacting with putative autoantigens, influenced by genetic susceptibility of both HLA associations and cytokine polymorphisms. The growing understanding of the cellular mechanisms involved in the effector immune response is already providing a rationale for more specific therapeutic approaches.

Vitreoretinal complications of osteoodontokeratoprosthesis surgery.

Purpose: To describe the vitreoretinal complications in a cohort of patients with osteoodontokeratoprosthesis (OOKP) and discuss surgical management. Methods: Review of notes of 35 OOKP cases performed at the Sussex Eye Hospital (Brighton, United Kingdom) between January 1999 and December 2005 was performed. Results: The overall incidence of vitreoretinal complications was 22.8%, which included vitreous hemorrhage (3 patients), rhegmatogenous retinal detachment (3 patients), endophthalmitis with retinal detachment complicating lamina resorption and optic extrusion (2 patients), and intraoperative choroidal hemorrhage (1 patient). Preexisting aphakia was associated with rhegmatogenous retinal detachment (P < 0.05, &khgr;2 = 4.36). Five patients required pars plana vitrectomy, which was performed either endoscopically (two cases) or using a binocular indirect viewing system (three cases) with one case requiring removal of the OOKP and insertion of a temporary keratoprosthesis. Retinal detachment repair was attempted on four of five patients but was successful for only one. Vitreous hemorrhage without retinal detachment required vitrectomy in one case, while two cases cleared spontaneously. Conclusions: Eyes receiving OOKP are prone to vitreoretinal complications, with retinal detachment associated with a poor prognosis. Thicker OOKP laminae and lamina bulk screening will hopefully reduce the risk of endophthalmitis due to unexpected resorption.

Measuring the effect of pars plana vitrectomy on vitreous oxygenation using magnetic resonance imaging

PURPOSE To study the effect of pars plana vitrectomy (PPV) on vitreous oxygenation (pO2) using magnetic resonance imaging (MRI). METHODS Patients due to undergo PPV for either macular hole or epiretinal membrane were recruited. MRI scanning was performed 1 week before and at least 3 months after PPV. MRI T1 mapping was performed using an inversion recovery-true fast imaging with steady-state precession (TrueFISP) sequence at several inversion times, from a single slice positioned through the center of both eyes in the axial oblique plane. Additional phantom data were measured in porcine vitreous, to define the relationships between T1 relaxation times and balanced salt solution (BSS), to simulate human vitreous and aqueous, respectively, for a suitable pO2 range (5-70 mm Hg). Pre-PPV pO2 was also measured intraoperatively using a polarographic oxygen probe. RESULTS Eleven participants (age range 59-84) were recruited; two declined the post-PPV scan. Corrected T1 times indicated that the mean (±SD) pO2 increased significantly following PPV, from 13.2 ± 5.8 to 34.5 ± 8.0 mm Hg (P < 0.001). In the nonsurgical (control) eye, pO2 did not change significantly from the first to second MRI scan (13.7 ± 7.8 vs. 16.3 ± 8.7 mm Hg, P = 0.239). Mean pO2 measured intraoperatively was 7.2 ± 0.6 mm Hg (n = 10). CONCLUSIONS These results confirm that vitrectomy substantially increases vitreous pO2. MRI is a noninvasive technique that can be used to study vitreous oxygenation in both vitrectomized and nonvitrectomized eyes.