Effect of Glial Cell Line-Derived Neurotrophic Factor on Retinal Function after Experimental Branch Retinal Vein Occlusion

Abstract

PURPOSE. The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.METHODS. Electrophysiological examination of the retina was performed in 20 pigs with standard and four-frame mfERG 4 weeks after induced BRVO and intravitreal injection of GDNF or vehicle. BRVO was induced by intraocular diathermia of the superior retinal vein. Inner retinal function was measured by analysis of the four-frame mfERG (iN1) and outer retinal function with standard mfERG (P1).RESULTS. In GDNF-treated BRVO eyes, P1 and iN1 amplitudes (P ¼ 0.51 and 0.78) or implicit times (P ¼ 0.08 and 0.99) did not differ from those in healthy fellow eyes. After vehicle injection, P1 and iN1 amplitudes of BRVO eyes were significantly lower than in the healthy fellow eye (P ¼ 0.022 and 0.013). The log ratios of mfERG amplitudes between experimental and healthy fellow eyes were calculated (BRVO/healthy). GDNF improved the ratios of the four-frame mfERG CONCLUSIONS. GDNF appears neuroprotective on retinal electrophysiological function after BRVO. The efficacy and safety of GDNF remain to be investigated in primate eyes. (Invest Ophthalmol Vis Sci. 2012;53:6207-6213)

Animal Models of Retinal Vein Occlusion

“…An alternative way to produce experimental BRVO is by using diathermy, which has been undertaken via a pars plana sclerotomy. 75,[120][121][122][123][124][150][151][152] In cats, BRVO has been induced with indirect ophthalmoscopy and 20gauge bipolar diathermy that is applied to the targeted vein/ veins for 5 seconds. [120][121][122][123][124] In pigs, a technique has been described that produces a BRVO following a temporal canthotomy, conjunctival incision, and performance of three sclerotomies at 10, 2, and 5 o'clock, 2 mm posterior to the corneal limbus.…”

“…[120][121][122][123][124] In pigs, a technique has been described that produces a BRVO following a temporal canthotomy, conjunctival incision, and performance of three sclerotomies at 10, 2, and 5 o'clock, 2 mm posterior to the corneal limbus. [150][151][152][153] In this method, a light source and a blunt bipolar diathermy probe are inserted into the vitreous and one or two major retinal veins are coagulated approximately 1 disc diameter away from the optic disc for 5 to 7 seconds after 5 seconds of compression and under direct view through an operating microscope and with the aid of a fundus contact lens. [150][151][152][153] This procedure does not involve vitrectomy.…”

“…[150][151][152][153] In this method, a light source and a blunt bipolar diathermy probe are inserted into the vitreous and one or two major retinal veins are coagulated approximately 1 disc diameter away from the optic disc for 5 to 7 seconds after 5 seconds of compression and under direct view through an operating microscope and with the aid of a fundus contact lens. [150][151][152][153] This procedure does not involve vitrectomy. [150][151][152][153] Intravitreal Injection of Substances.…”

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs

“…Consequently, the appearance of the response measured as IC in our porcine model differs from the human IC measured by Shimada et al 12 The appearance of the signal is identical to porcine recordings with the same recording settings, previously published by our group. 14,37,38 The visual streak was identified by alignment of the infrared picture and the fundus image and defined as a band, four hexagons high, stretching horizontally one hexagon above the optic nerve head. The slope of the changes in the mfERG amplitudes with TTX as a function of time in anesthesia was compared to the slope of the amplitude in the anesthesia-only recordings.…”

Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model

“…For each study eye, the average P1 and IC amplitudes from the visual streak were extracted and compared to the corresponding area of the right normal eye recorded at the same session. Using these ratios, we minimized the effect of interindividual and day-to-day variance often seen in mfERG recordings (Christiansen et al 2012a;Ejstrup et al 2012). Based on mfERG topography and fundus images, the visual streak was, as previously, identified on aligned infrared and fundus images as a four mfERG stimulation hexagon tall band stretching horizontally just superior of the optic disc.…”