Retinal mechanisms mediating vision

Thursday, October 14, 12:00 – 14:00 ET // Register here

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Serial electron microscopy and high density electrophysiology together have provided new insight into the retinal circuit mechanisms shaping vision in the macula. In this session, experts in the area will review recent research on retinal mechanisms mediating high acuity spatial and color vision, spanning the entire cascade of circuits connecting cone photoreceptors to retinal ganglion cells.

This special session is being hosted by the Clinical Vision Sciences Technical Group, the Color Technical Group, and the Vision Technical Group along with the Fall Vision Meeting Planning Committee.

Invited Speakers:

• Raunak Sinha, University of Wisconsin – Madison

• Wei Li, National Eye Institute, National Institutes of Health

• Chi Zhang, University of Washington

• Sara Patterson, University of Rochester

Moderators:

• Jesse Schallek, University of Rochester

• Ramkumar Sabesan, University of Washington

Abstracts:

Light adaptation in primate fovea

Raunak Sinha, Department of Neuroscience, University of Wisconsin, USA

Our visual performance varies remarkably across space. For instance, our central vision exhibits the highest spatial and chromatic sensitivity, whereas temporal sensitivity is higher for our peripheral than central vision. Our high-acuity central vision is initiated in the cone photoreceptors which are packed in a dense array in the fovea. The density and morphology of cones differ remarkably between foveal and peripheral primate retina, but our knowledge about their functional differences remain quite poor. In the past we have shown that cone signals in the fovea are two-fold slower than in the peripheral retina consistent with the difference in the temporal sensitivity of cone-mediated vision to high-frequency flicker. But we are far from understanding the full breadth of these topographic differences in cone signaling across primate retina over a wide range of light inputs. I will present recent results of a detailed comparison of functional properties - such as kinetics, gain and cellular noise - of cones in the fovea with that in rest of the primate retina. I will show how foveal cones adapt across a wide range of luminance and if they exhibit differences in the amplitude, kinetics or timescales of adaptation when compared to cones in the peripheral primate retina. Lastly, I will share our findings on the relative contribution of cone vs circuit mechanisms towards luminance adaptation in the dominant neural circuit in the fovea - the midget ganglion cell pathway.

Funding Acknowledgement: NIH grants (EY026070, EY031411), BrightFocus Foundation, McPherson Eye Research Institute.

Mitochondria in cone photo-receptors act as microlenses to enhance photon delivery and confer directional sensitivity to light

Wei Li, Retinal Neurophysiology Section, NEI, NIH

Mitochondria are cellular organelles chiefly intended for energy production. Mammalian photoceptors aggregate numerous mitochondria in the ellipsoid region immediately adjacent to their light-sensitive outer segments to support the high metabolic demands of phototransduction. However, these complex, lipid-rich organelles are also poised to affect the passage of light into the outer segment, an essential step in the transduction of physical energy into cellular signals. Here we show, via live-imaging and computational modeling, that despite this risk of light scattering or absorption, such tightly packed mitochondria concentrate light for entry into the outer segment. Intriguingly, this “microlens”-like feature of cone mitochondria delivers light with an angular dependence akin to the Stiles-Crawford effect (SCE), providing a simple explanation for this essential visual phenomenon that improves resolution. Given the pivotal role that photoreceptor mitochondria play in multiple retinal degenerative diseases, this new insight into their optical properties provides critical information for the accurate interpretation of non-invasive ophthalmic imaging results and lends support for using SCE as an early diagnostic tool.

Funding Acknowledgement: NEI Intramural Research Program.

Circuit remodeling during development shapes the human foveal midget connectome for high visual acuity

Chi Zhang, Department of Biological Structure, University of Washington, USA

In the human fovea, the midget circuitry shows a ‘private-line’ design, which contributes to the high visual acuity by preserving visual signals at single-cone resolution. Each foveal midget ganglion cell is often contacted by a midget bipolar cell that receives input from a single cone photoreceptor. Developmental strategies creating the private-line are unknown. The creating the private-line are unknown. The connectivity could be rapidly set up with extreme precision as early as synaptogenesis or, by contrast, gradually shaped in concordance with the maturation of foveal architecture and visual sensitivity. To test these hypotheses, we reconstructed the developing midget circuitry in the fetal human fovea using block-face serial electron microscopy. The results suggest that the foveal midget circuitry requires synaptic remodeling to reach the non-divergent connectivity. The circuitry is sculpted from excessive convergent and divergent connections early in fetal life, to each midget bipolar cell contacting a single cone by mid-gestation. The bipolar cell - ganglion cell connectivity undergoes a more protracted period of refinement.

The S-cone connectome of the primate retina

Sara S. Patterson, Center for Visual Science, University of Rochester, Rochester, NY

Trichromatic humans have three types of cone photoreceptor: L-, M- and S-cones, which are tuned to long-, medium- and short-wavelength light, respectively. We know the least about the pathways carrying signals from S-cones because they are very rare and make up less than 10% of all cones. Past research has focused primarily on small bistratified ganglion cells that compare the outputs of S-cones to the summed outputs of L- and M-cones (S vs. L+M). I will review our recent efforts to comprehensively map S-cone circuitry within the macaque central retina using serial block-face scanning electron microscopy. We identified a surprising diversity of S-cone ON and OFF pathways, each with the same spectral signature: S vs. L+M. In total, the primate retina conveys this one spectral signal to the brain along at least five parallel pathways. Our results challenge classic color vision models that can only account for a single S vs. L+M pathway and demonstrate how our visual systems use color information for far more than just color perception.

Funding Acknowledgement: F32-EY032318, R01-EY027859, P30-EY001730.