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

2

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

4

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

5

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

6

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?

9

Unusual retinal gangion cells

10

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

13

Light hyperpolarizes the cell

14

cGMP channels are open in the dark

15

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

21

Turning off Rhodopsin

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Turning off GPCRs

23

Turning off the G protein

24

Mice without GAP cannot turn off light response quickly

no GAP

with GAP (wild-type)

25

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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