Seminar: Photoreceptor Energy Metabolism Directs Neovascular Retinal Disease

Lois E. H. Smith, Professor of Ophthalmology at Harvard Medical School, Boston Children’s Hospital will be delivering a seminar on “Photoreceptor Energy Metabolism Directs Neovascular Retinal Disease” on Wednesday, March 14th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: Neuronal energy demands are met by a tightly coupled and adaptive vascular network that supplies nutrients and oxygen. The retina is one of the highest energy-consuming organs, exceeding the metabolic rate of the brain; blood vessels grow and regress in reaction to changes in these high demands. Reduced nutrients and reduced oxygen availability instigate compensatory albeit misguided pathological neovascularization in proliferative retinopathies. Conversely, impaired retinal ganglion cell and photoreceptor survival are correlated with abrogated vascular development and as neurons degenerate, the retinal vasculature atrophies to match the reduced metabolic requirements. In mice, photoreceptor degeneration is associated with thinning of the choroid and inner retinal blood vessels. Conditions such as diabetic retinopathy, vaso-proliferative retinopathy of prematurity and neovascular age-related macular degeneration (AMD) have been characterized as diseases of the vasculature. However, it is becoming more evident that the metabolic needs of the neural retina profoundly influence blood vessel supply in development and in disease.

Retinal oxygen sources and the vaso-proliferative response to low oxygen levels have been well characterized. However, understanding the specific fuels used in the retina to generate ATP and supply building blocks for biosynthesis, as well as understanding the vaso-proliferative response to the lack of fuel are also key to neurovascular development. The metabolic and energy needs of the retina have been assumed to be met by glucose, as the retina is part of the CNS, and the brain relies almost exclusively on glucose. There are two primary pathways that cells can use to generate ATP from glucose, glycolysis and oxidative phosphorylation. However, Cohen and Noell concluded in 1960 that a substantial portion of the energy produced through oxidation by the retina (around 65%) was not derived from glucose. We recently showed that the retina (photoreceptors) can also oxidize lipid through fatty acid β-oxidation to produce ATP, accounting for the energy gap noted by Cohen. Both glucose and lipid metabolism are forces that shape the vascular supply of the eye in development and in vaso-proliferative eye diseases.

Seminar: Molecular Organization of the First Visual Synapse

Seminar Flyer-Martemyanov

Kirill Martemyanov, Associate Professor at the Scripps Institute will be delivering a seminar on Molecular Organization of the First Visual Synapse, on Wednesday, February 10th at 12pm in the Moran Eye Center auditorium.

Abstract: Signaling in the retina plays an essential role in our vision. Light is detected by rod and cone photoreceptors that convert it to the electrical response further propagated through the retina circuitry by means of synaptic communication between neurons. To be able to see at low light levels, highly sensitive rods must faithfully transmit the signal that they generate to downstream bipolar neurons. The efforts in my laboratory are focused on studying molecular players and signaling events at the first visual synapse between formed by rod photoreceptors. I will describe how multiple elements of the synaptic signaling machinery are organized and scaffolded together to ensure proper transmission of signal generated by rods enabling vision at low light.

Seminar: Protein Diversity Through Modification – Role In Photoreceptor Function

Flyer Dr Visvanathan

Ramamurthy Visvanathan from West Virginia University will be delivering a seminar on Protein diversity through modification and its role in photoreceptor function on January 21st, 2015  in the Moran Eye Center auditorium.

Abstract:  The enormous diversity of proteins despite limited number of genes is generated by post-transcriptional processing of the pre-mRNA. Post- translational modifications further expand the diversity of protein, its properties and functions. In this talk, I will focus on one such post- translational protein modification, prenylation, a lipid attachment and post-prenyl processing and its importance in photoreceptor cell function. I will also talk about our recent collaborative work on understanding how alternative pre-mRNA splicing generates proteins unique to photoreceptor cells from otherwise ubiquitously expressed genes.

Seminar: Jiang Li, Intraflagellar Transport (IFT) Essential For Photoreceptor Connecting Cilium/Axoneme Formation and Maintenance

Seminar Flyer-Jiang Li.pptx

Jiang Li will be delivering a seminar, Intraflagellar Transport (IFT) Essential For Photoreceptor Connecting Cilium/Axoneme Formation and Maintenance on Tuesday, August 19th, 2014 in the John A. Moran Eye Center auditorium.

 

Abstract:

A light-sensitive photoreceptor outer segment (OS) is a modified primary cilium and communicates with the inner segment (IS) through a “connecting cilium” (CC), a structure equivalent to the transition zone of primary cilia. Anterograde intraflagellar transport (IFT) has been implicated in protein trafficking of photoreceptor sensory cilia. IFT is a bidirectional ciliary trafficking pathway conserved between invertebrates and vertebrates with heterotrimeric (KIF3) and homodimeric (KIF17) kinesin-II as anterograde motors. To differentiate anterograde IFT func,on in photoreceptor development and survival, we generated embryonic retina-specific and postnatal tamoxifen-induced deletions of KIF3a, and germline deletions of KIF17. In embryonic retina-specific Kif3a knockout mouse, basal bodies docked to the cortex of mutant photoreceptors but failed to form CC and OS. Rhodopsin, cone pigments and other OS proteins were retained in the knockout photoreceptor IS. In contrast, tamoxifen- induced deletion of Kif3a in adult mouse led to slowly progressing photoreceptor degeneration due to the inability of photoreceptors to maintain their mature axonemes. Rhodopsin and cone pigments trafficked to OS up to 3 weeks post- induction. Once fully mature, the Kif3a knockout photoreceptor axonemes were unable to be maintained and disintegrated slowly. Germline deletion of KIF17 affected neither axoneme structure nor photoreceptor morphology/function, thereby excluding an essential role of KIF17 in photoreceptor IFT. Our results demonstrate that IFT is not required for rhodopsin transport to the OS. Rather, anterograde IFT mediated by KIF3a, but not by KIF17, participates in photoreceptor transition zone (PTZ)/axoneme formation and maintenance.

Seminar: Ocular Consequences of Stra6 (Retinol-Binding Protein Receptor) Gene Disruption In Mice

Dean Bok from University California Los Angeles is delivering a seminar on October 24th, 2012 in the Moran Eye Center auditorium on the first floor.  Dean will be talking about Ocular Consequences of Stra6 (Retinol-Binding Protein Receptor) Gene Disruption In Mice.

Abstract: We generated a mouse modelin in which the Stra6 gene was functionally disrupted to facilitate the study of visual responses, changes in ocular morphology and retinoid processing under STRA6 protein deficiency.  Western blot and immunocytochemistry were used to determine expression of STRA6 protein.  Visual responses and morphological studies were performed on 6 week, 5 month and 10 month old mice.  The retinoid content of eye tissues was evaluated in dark adapted mice by high performance liquid chromatography.  Our studies of Stra6 -/- mice established the importance of the STRA6 protein for the uptake, intracellular transport and processing of retinol by the RPE.  In its absence, rod photoreceptor outer and inner segment length was reduced as were scotopic responses, but rod cell number remained stable.  Cone cell numbers were reduced as were photopic responses.  STRA6 was also required for dissolution of the primary vitreous.  It was clear from these studies that, due to low but persistent levels of retinoids and a stable rod population, STRA6 is not the only pathway for retinol uptake by the RPE.

Seminar: Photoreceptor Networks And Color

Julie Schnapf, Ph.D. from University California San Francisco is delivering a seminar this Wednesday, September 12, 2012 at the Moran Eye Center auditorium on the first floor.  Julie will be talking about Photoreceptor Networks and Color.

Abstract:  Photoreceptors are more than just photon transduction machines.  They also communicate with each other, forming interactive electrical networks that increase visual sensitivity and create color-opponency.  These network interactions help explain some puzzling observations about color perception.

Review: Defective Trafficking of Rhodopsin and Its Role In Retinal Degenerations

This is a great review paper on the role of rhodopsin trafficking and its influence on retinal degenerative disease by TJ Hollingsworth and Alecia Gross.  Rhodopsin delocalization in rod photoreceptors has been recognized for some time as one of the first indications of retinal photoreceptor cell stress in retinal degenerative diseases, so I was intrigued when seeing this paper come up in PubMed.   Continue reading “Review: Defective Trafficking of Rhodopsin and Its Role In Retinal Degenerations”