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Purpose. To develop a middle-sized animal model of outer retinal degeneration and to evaluate the effectiveness of suprachoroidal-transretinal stimulation (STS) in eliciting cortical potentials from this model. Methods. Twelve rabbits were intravenously injected with 0.47 mg/kg verteporfin and the retinas were irradiated with a red light for 90 minutes. Fluorescein angiography and full-field and focal electroretinography (ERG) were performed at 7 and 28 days after the irradiation. Electrically evoked potentials (EEPs) were elicited by electrical stimulation, with the STS electrode implanted over the irradiated region, 1 month and 1 year after the irradiation. EEPs were also recorded from three rabbits before and after retinotomy of the normal retina surrounding the degenerated area, to eliminate the influence of stray currents. The retina beneath the site of the STS electrode was examined histologically at 1 month (group 1) and 1 year (group 2) after the irradiation. Results. An extensive area of degeneration was detected histologically, mainly in the outer retina after the irradiation. Focal ERGs were not recorded when the stimulus was confined to the irradiated area; however, EEPs were successfully elicited by STS of the same area 1 month and 1 year after the irradiation. The 360 degrees retinectomy did not significantly alter the amplitudes, the implicit times, or the thresholds of EEPs evoked by STS. Conclusions. Verteporfin with light irradiation induces degeneration predominantly in the outer retinal layers in rabbits. The elicitation of EEPs by STS from the degenerated area suggests that the STS system may be useful in patients with retinitis pigmentosa.

Purpose: Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair., Methods: Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed., Results: Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05-0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-alpha when compared to control medium; SDF-1 remained unchanged., Conclusions: The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment.

Purpose: A prior study showed that brain-derived neurotrophic factor (BDNF) rescues photoreceptors from collateral retinal damage caused by photodynamic therapy (PDT). This study was conducted to determine whether ciliary neurotrophic factor (CNTF), a combination of BDNF and CNTF, or pigment epithelial cell-derived growth factor (PEDF) might protect photoreceptors and retinal function more effectively than BDNF. Also investigated was whether protection would be observed after a second round of PDT with adjunctive BDNF treatment., Methods: Normal rats received intravitreal injections of BDNF, CNTF, a combination of BDNF and CNTF, or PEDF in one eye and PBS in the other 2 days before PDT. Retinal function and photoreceptor survival were assessed with multifocal ERG (mfERG) and histology 1 week after PDT. Another group of rats received two courses of PDT 3 months apart, with injection of BDNF 2 days before each treatment., Results: All factors significantly increased photoreceptor survival. The combination of BDNF and CNTF rescued more photoreceptors than either factor alone. Only BDNF improved retinal function 1 week after PDT, with CNTF and the combination of BDNF and CNTF reducing mfERG responses. BDNF injection before a second round of PDT improved mfERG responses and retinal structure., Conclusions: BDNF is the most effective single factor among those tested for neuroprotection and improvement of retinal function after PDT, although a combination of BDNF and CNTF rescues more photoreceptors. Adjunctive treatment with BDNF also protects retinal structure and function through two rounds of PDT, suggesting its potential value for patients who require multiple treatments.

Purpose: Verteporfin photodynamic therapy (PDT) is the most effective treatment for age-related macular degeneration, using laser activation of a photosensitizing dye to achieve closure of choroidal neovascularization. Although PDT preferentially affects pathologic vessels, it can also cause collateral damage to the overlying retina. In the current study, it was found that the neuroprotective agent brain-derived neurotrophic factor (BDNF) reduces this retinal damage., Methods: Normal adult rats received intravitreal BDNF in one eye and PBS or no injection in the other eye 2 days before PDT., Results: Control eyes exhibited choroidal hypofluorescence, moderate to severe photoreceptor loss, and depression of local retinal function measured using multifocal ERG in the laser-treated area. BDNF-injected eyes had more surviving photoreceptors and improved multifocal ERG responses 1 week after PDT. BDNF did not diminish the effect of PDT on the choroidal circulation as assessed by fluorescein angiography, and there was no evidence of retinal toxicity due to BDNF treatment., Conclusions: These results suggest that adjunctive neuroprotective therapy may reduce collateral damage to photoreceptors and improve visual outcome after PDT.