How the eye sees
Last timeAnatomy of the eyeCells in the retinaRods and conesVisual receptors
This timeVisual receptorsVisual transduction
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Structure of the eye
The Basic Retinal Circuit
1. Receptor Cells(rods and cones)
2. Bipolar Cells
3. Ganglion Cells
Different cells in the retina
Back of eye
Front of eye
4. Horozontal Cells
5. Amacrine Cells
6. Pigment cells
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Photoreceptor cells are the light sensors
Back of eye
Front of eye3
The visual receptors are G Protein Coupled Receptors
• seven transmembrane regions
• hydrophobic/ hydrophilic domains
• conserved motifs• chromophore stably
attached to receptor
(Schiff’s base Lys296 in TM7)• thermostable
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Different opsins recognize different wavelengths
We have 4 different opsins
Rods: Rhodopsin: blue/green sensitive pigmentCones: S opsin: blue sensitive
M opsin: green sensitiveL opsin: red sensitive
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The light catcher is 11-cis-retinal
• covalently attached to opsin GPCR
• Vitamin A derivative
• Binds light, changes conformation from 11-cis to all-trans
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Rhodopsins are packed in a crystalline array in the disc
Atomic force microscopy
10 rhodopsins/cell8
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They even make other cells do their work:Pigment cells recycle retinal
Interphotoreceptor binding proteinCarries retinal to pigment cell
Retinal modified to 11-cisCombines with opsin to form rhodopsin
Pigment cell
Photoreceptor
+
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What happens if all rods and cones are killed?
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Unusual retinal gangion cells
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Retinal Ganglion cells express melanopsin, are sensitive to light
and project to the superchiasmatic nucleus
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Signal Transduction in Photoreceptor Cells
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Rods respond to single photons of light
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Light hyperpolarizes the cell
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cGMP channels are open in the dark
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The visual cascade is a G protein-coupled cascade
Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels
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Signal transduction in the dark
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Signal transduction in the light
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High amplification in the visual cascade
Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels
1 100 100 100,000 1000?
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Phototransduction is a highly regulated cascade
Adapt to respond over 6 log orders of light
1. Long-term adaptation-pupil size
-receptor photobleaching
2. Short-term adaptation -recovery of membrane potential -deactivation of receptors
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Negative regulation of phototransduction
Rhodopsin Gtransducin phosophodiesterase cGMP to GMP close cGMP channels
Rhod kinase GAP Guanylate cyclase GTP to cGMP open channelsArrrestin
Drop in Ca influx activates Ca dissociates from Calmodulin,
Opens channels
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Turning off Rhodopsin
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Turning off GPCRs
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Turning off the G protein
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Mice without GAP cannot turn off light response quickly
no GAP
with GAP (wild-type)
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Phototransduction: Differences between rods and cones
Rods ConesVery sensitive to light 30x less sensitive to light
each rhodopsin activates 30x less G proteins
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Properties of phototransduction
• responds to 1 photon of light• responds over a range of 6 log orders of light• responses are extremely reliable
•1000s of discs maximize surface area of light detection• high concentration and thermostability of rhodopsin means high detection, low noise• adaptation increases the operating range
Photoreceptors are highly specialized to detect light!
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