William D. Eldred
Professor of Biology
Graduate Program in Neuroscience, and Program in Molecular Biology, Cell Biology and Biochemistry
My research for the past 15 years has focused on the role of the gaseous neuromodulator nitric oxide (NO) in retinal signal transduction and ocular pathology. We have determined that NO is reciprocally related to many retinal neurotransmitters including GABA, glycine, acetylcholine, and dopamine in that NO modulates their release and they in turn modulate NO production. We have also shown that every cell type in the retina can normally produce NO. Using direct imaging of NO, we have established that in retina and hippocampus that NO is not freely diffusible. We have examined the role that NO plays in the early neuronal cell death seen in diabetic retinopathy. We focused on the role that the signaling peptide adrenomedullin plays in producing the pathological increases in NO found in early diabetic retinopathy. We established and localized all of the biochemical steps in this pathway and we found a pharmacological intervention that inhibits the pathological activation of the adrenomedullin/NO signaling pathway. Since both NO and adrenomedullin are involved in much ocular pathology including glaucoma, ischemia, and uveitis, a better understanding of the adrenomedullin/NO signaling pathways may have broad clinical applicability. More recently we have been focusing on the cellular signaling pathways that are involved in traumatic brain injury using the retina and in vitro brain cultures as model systems. We are examining a number of neurochemical markers that are modulated by blast in brain. By using the retina and culture systems that are extremely well characterized anatomically, physiologically and neurochemically, we can determine the underlying signaling pathways that are responsible for the pathology. This will allow us to develop both prophylactic and post-blast treatment strategies to reduce the pathology produced by blast in both retina and brain.
- BI 108 Introductory Biology
- BI 755 Cellular and Systems Neuroscience
- Blom J, Giove T, Deshpande M, Eldred WD. (2012). Characterization of the nitric oxide signaling pathways in the mouse retina. J. Comp. Neurol. 520:4204-4217.
- Blom J, Giove TJ, Pong WW, Blute TA, Eldred WD. (2012). Evidence for a functional adrenomedullin signaling pathway in the mouse retina. Mol. Vis. 18:1339-1353.
- Blom JJ, Giove T, Favazza T L, . Akula J D, Eldred WD (2012) Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy. J. Ocular Biol. Diseases and Informatics 2011, Volume 4, Numbers 1-2, Pages 70-82.
- GioveTJ, Sena-Esteves M, Eldred WD. (2010). Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection. Exp. Eye Res., 91:652-659.
- Giove TJ, Deshpande MM, Gagen CS, Eldred WD (2009). Increased neuronal nitric oxide synthase activity in retinal neurons in early diabetic retinopathy. Mol Vis. Nov 9;15:2249-58.
- Blom JJ, Blute TA, Eldred WD (2009). Functional localization of the nitric oxide/cGMP pathway in the salamander retina. Vis Neurosci 26:275-286.
- Giove TJ, Deshpande MM, Eldred WD (2009). Identification of alternate transcripts of neuronal nitric oxide synthase in the mouse retina. J Neurosci Res .Epub.
- Pong WW, Eldred WD (2009). Interactions of the gaseous neuromodulators nitric oxide, carbon monoxide, and hydrogen sulfide in the salamander retina. J Neurosci Res 87:2356-2364.