Different states of energy metabolism in the vertebrate retina can be identified by stimulus-related changes in near UV transmission.

BACKGROUND: Our aim was to identify different states of energy metabolism in the perfused isolated vertebrate retina by simultaneous recordings of light-evoked changes of transretinal potential (TRP) and spectroscopic changes related to oxidation of pyridine nucleotides. METHODS: Isolated retinas were obtained from R.esc. and superfused. For each setting, three experiments were performed. Eighteen retinas were used. TRP as a response to light stimulation was recorded simultaneously with stimulus-induced transmission shift at 350 nm. These responses were recorded under normal conditions, under withdrawal of oxygen and glucose, and after addition of electron transport inhibitors and uncouplers of oxidative phosphorylation. RESULTS: Under normal conditions, TRP was strongly correlated with transmission shift after light stimulation. Without oxygen, amplitudes of stimulus-related TRP decreased and response related increase of transmission at 350 nm was reduced. The retina showed a much higher general absorption of the analyzing light. During glucose lack, an overall increase in transmission at 350 nm could be observed. The addition of Amytal yielded a specific reduction of the OFF components. Cyanide attenuated the ON and OFF components. Dinitrophenol yielded a considerable loss of the electrical ON response. Transmission change was affected less than electrical signal. Chlorophenylhydrazine induced a reproducible reduction of electrical responses, with a relative increase of transmission shift at 350 nm. CONCLUSION: In the isolated perfused retina, different states of energy metabolism and their specific impact on neuroretinal responses can be examined by simultaneous recordings of stimulus-related neuronal activity and spectroscopic changes.

A method and technical equipment for an acute human trial to evaluate retinal implant technology.

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 microm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

Cortical activation via an implanted wireless retinal prosthesis.

PURPOSE: To demonstrate local cortical activations in the primary visual cortex of the cat as a result of retinal electrical stimulation by means of a completely wireless-controlled, implantable retinal prosthesis in a series of acute experiments. METHODS: The transfer of energy to drive the device and signals to activate any combination of 25 retinal electrodes was achieved completely wirelessly by an external transmitter positioned in front of the eye. Individually configured electrical stimuli were applied via any combination of 25 electrodes, on sending the necessary pulse parameters to the implant. Placement of the implant onto the retinal surface was achieved after lensectomy and vitrectomy in the cat. Fixation was performed with a retinal tack. Cortical activation patterns were recorded by means of optical imaging of intrinsic signals. RESULTS: Implantation and fixation were successfully performed in three cats. Wireless activation of the implant by radiofrequency was demonstrated by recording of stimulus artifacts from the sclera. Local activation of the visual cortex measured by optical imaging of intrinsic signals revealed a shift of cortical response that was well correlated with a change in the position of the activated retinal electrodes. CONCLUSIONS: The results demonstrate the retinotopic activation of the visual cortex using a completely wireless, remote-controlled retinal implant.

Pharmacokinetics and safety of intravitreally delivered etanercept.

BACKGROUND: The anti-inflammatory drug etanercept may be an effective therapeutic agent in diabetic retinopathy. In order to further evaluate its potential, the pharmacokinetics and safety of this drug after intravitreal delivery were investigated. METHODS: After intravitreal administration of etanercept in rabbits, clinical examination, electroretinography (ERG), visually evoked potentials (VEP) and histology were evaluated. The pharmacokinetics and distribution of etanercept were analyzed using fluorescence-coupled protein at 0, 2, 4, and 8 weeks after injection in vitreous, retina, and choroid. RESULTS: No adverse effects and signs of toxicity were found. Etanercept showed peak concentrations after 4 weeks in the retina and choroid. CONCLUSIONS: Intravitreally delivered etanercept is safe and results in high concentrations in the retina and choroid over a long period of time.

Electro-oculographic findings after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in age-related macular degeneration.

PURPOSE: To evaluate potential electro-oculographic changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age-related macular degeneration (AMD) in a randomised comparative (self-controlled) trial. METHODS: A consecutive series of 30 patients suffering from subfoveal choroidal neovascularisation secondary to age-related macular degeneration underwent 360 degrees retinotomy and macular translocation. The EOG served as the main parameter of the study and was recorded 1 day prior to the translocation surgery and no earlier than 21 days after the silicone oil removal. RESULTS: Postoperatively, a statistically significant decrease in mean dark trough by 64% was found for treated eyes (P<0.001). The mean dark trough of the fellow eye remained stable after surgery (P=0.33). The postoperative difference between the treated und untreated eyes proved to be statistically significant (P<0.001). The Arden ratio remained stable in the treated and untreated eyes with mean values of 204% (P=0.81) and 213% (P=0.18), respectively. A significant correlation between the reduction of the dark trough and the visual acuity at the 1-year follow-up was found. CONCLUSIONS: A persistent decrease in the corneofundal potential is associated with 360 degrees retinotomy and macular translocation for exudative AMD. This indicates a substantial postoperative malfunction of retinal pigment epithelial cells and an impaired photoreceptor regeneration. The impeded recovery of the RPE-photoreceptor complex can be interpreted as the result of the surgical trauma on the basis of prediseased RPE. A severe postoperative decrease in dark trough forecasts an incomplete recovery of visual acuity.