The scotopic threshold response of the cat erg is suppressed selectively by GABA and glycine

Corneal electroretinograms (ERGs) were recorded from anesthetized cats under scotopic conditions. We examined whether the scotopic threshold response (STR) of the ERG could be functionally distinguished from scotopic PII and a-wave using intravitreal application of neuroactive agents. We found that neurotransmitters with active sites on third order neurons had several different effects. Results were: (1) glycine and [gamma]-amino butyric acid (GABA) selectivity suppressed the STR but had relatively small and/or opposite effects on PII; (2) serotonin, acetylcholine and dopamine were nonselective and suppressed both STR and PII; (3) strychnine blocked the suppression of the STR by glycine. GABA-a antagonists alone only partially blocked GABA effects on the STR, and GABA-b antagonists were ineffective; (4) strychnine enhanced the STR. Bicuculline also increased STR amplitudes, but only in the presence of haloperidol. Our results suggest that the retinal pathway that contributes to the rod-driven STR is strongly influenced by cells that release glycine or GABA in the dark. These cells are possibly third order neurons in the retina. Our results also suggest that picrotoxin and bicuculline can facilitate the release of dopamine in the cat retina. Furthermore, the data indicate a light evoked release of dopamine which was first noticeable at about two log units above ERG threshold.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29513/1/0000600.pd

Assessment of foveal cone photoreceptors in Stargardt's macular dystrophy using a small dot detection task

We measured frequency-of-seeing curves for tiny (1.125 and 3.375 min arc) stimuli flashed briefly at absolute threshold to estimate the density of foveal cones in normals and in subjects with Stargardt's macular dystrophy. Foveal absolute thresholds for Stargardt's were elevated 1.5 log units over normal. Analysis using Poisson counting statistics indicated that the quantal absorption to stimulate individual cones was normal for Stargardt's but that effective optical density of individual cones was reduced by > 1 log. Numerical density of foveal cones was reduced 1 log unit for Stargardt's patients with acuities of 20/30-20/100.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30727/1/0000376.pd

Translational Retinal Research and Therapies.

The following review summarizes the state of the art in representative aspects of gene therapy/translational medicine and evolves from a symposium held at the School of Veterinary Medicine, University of Pennsylvania on November 16, 2017 honoring Dr. Gustavo Aguirre, recipient of ARVO's 2017 Proctor Medal. Focusing on the retina, speakers highlighted current work on moving therapies for inherited retinal degenerative diseases from the laboratory bench to the clinic

Chapter 6 Negative components of the electroretinogram from proximal retina and photoreceptor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29553/1/0000641.pd

RanBP2 Modulates Cox11 and Hexokinase I Activities and Haploinsufficiency of RanBP2 Causes Deficits in Glucose Metabolism

The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(−/−) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/−) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies