D. Imai

Intraocular gene transfer of pigment epithelium-derived factor rescues photoreceptors from light-induced cell death

In this study, we investigated whether intraocular gene transfer of pigment epithelium‐derived factor (PEDF) ameliorates the extent of light‐induced photoreceptor cell death. Lewis rats received intravitreous injection of 3 × 109 particles of adenoviral vector expressing PEDF (AdPEDF.11) in one eye and 3 × 109 particles of empty adenoviral vector (AdNull.11) in the contralateral eye. The rats were then dark‐adapted for 3 days after which they were continuously exposed to fluorescent light (2,500 lux) for 0, 6, 24, 96, and 168 h. Both eyes were then enucleated and processed for morphometric analysis. Cell death in the retina was examined using TUNEL staining with a propidium iodide counterstain. The photoreceptor cell counts in each of the three groups were significantly different (P < 0.001). Eyes that received intravitreous injection of AdNull.11 or no injection showed a greater number of pyknotic photoreceptor cells and a reduced photoreceptor cell density as compared to eyes treated with intravitreous AdPEDF.11 injection. AdNull.11 treated eyes showed a lesser but still significant protection of photoreceptor cells when compared to untreated eyes. Fewer TUNEL‐positive photoreceptor cells were present in AdPEDF.11 treated eyes than in AdNull.11 treated or untreated eyes (P = 0.004). The amplitudes of the ERG a‐wave, b‐wave, and oscillatory potentials (OPs) were increased significantly by treatment (P < 0.05). These data suggest that adenovirus vector‐mediated intraocular expression of PEDF significantly increases photoreceptor cell survival following excessive light exposure. Neuroprotection may result from inhibition of light‐induced apoptotic processes. This study provides proof of concept for a gene transfer approach to modulating retinal cell death resulting from photo‐oxidative damage and supports the hypothesis that gene transfer of PEDF is broadly applicable to modulating apoptosis in the retina.

Transpupillary thermotherapy: effect of wavelength on normal primate retina.

Purpose: To correlate changes in primate fundus after transpupillary thermotherapy (TTT) at two wavelengths. Methods: Twelve primate eyes were treated with TTT using a wavelength of 635 nm (n = 7) or 810 nm (n = 5). Laser parameters were as follows: 635 nm (spot size, 1 mm; duration, 30–80 seconds; and fluence [power over time], 20–91.4 J/cm2) and 810 nm (spot size, 2 mm; duration, 60 seconds; and fluence, 96–436 J/cm2). Fundus photography, fluorescein and indocyanine green angiography, and enucleation were performed at time 0 or 2 weeks after TTT for histologic analysis. Results: Threshold for fundus lesions (91.4 J/cm2 at 635 nm and 191 J/cm2 at 810 nm), acute and chronic retinal damage shown by histologic analysis (79.2 J/cm2 at 635 nm and 96 J/cm2 at 810 nm), and choroidal vessel occlusion (50 J/cm2 at 635 nm and 96 J/cm2 at 810 nm) were lower at 635 nm. Disorganization of the retina and retinal pigment epithelium was seen for both wavelengths at time 0 and 2 weeks after TTT. Occlusion of the choriocapillaris and choroidal stromal vessels was noted only in specimens obtained 2 weeks after TTT. Conclusions: TTT resulted in acute and delayed damage to the neurosensory retina that persisted at 2 weeks. The 635-nm wavelength demonstrated a lower threshold fluence for visible fundus lesions, retinal damage, and choroidal vascular occlusion than the 810-nm laser.

Retinal Adaptability Loss in Serous Retinal Detachment with Central Serous Chorioretinopathy

PURPOSE To investigate the functional characteristics of the detached retina on a serous retinal detachment (SRD) in eyes with central serous chorioretinopathy (CSC) with spared visual acuity. METHODS Multifocal electroretinograms (mfERGs) were recorded with a long recording time of 14 minutes, 34 seconds, to obtain accurate measurement of the second-order kernel (K2.1), an index of functional adaptability of the retina, from seven eyes with CSC (visual acuity, >or=1.0). The first-order kernel (K1) and the K2.1, elicited by stimulating the area of the SRD, were compared with those from the corresponding areas in eyes of 15 age-matched volunteers (controls) and in 6 eyes of patients with diabetic retinopathy (DR) that have been reported to have a K2.1 attenuation. RESULTS K2.1 was essentially flat in the SRD eye. The K2.1 amplitude and log-scaled amplitude ratio of K2.1 to K1 (K2.1/K1) were severely reduced (to <95% confidence interval [CI] of control levels) in all eyes. The value of K2.1/K1 of the SRD was less than that in any of the control and DR eyes. K1 was moderately reduced but was not smaller than the 95% CI of control eyes. The mfERGs from the area without the SRD and those from the fellow eyes did not differ significantly from those in control eyes. CONCLUSIONS A possible cause of the flat K2.1 observed on the SRD is the separation of the sensory retina. A substantial disparity between the recovery of cones and rods could contribute to the loss of retinal adaptability, resulting in the flat K2.1 as well as the unique visual impairments in CSC eyes.