PolyU Retinal Physiology Lecture Notes PDF

PolyU Retinal Physiology Professor LIN School of Optometry 1 Review on previous lecture: 2 Review on previous lecture: Ø It is the center of the eye's sharpest vision (the greatest visual acui...

PolyU Retinal Physiology Professor LIN School of Optometry 1 Review on previous lecture: 2 Review on previous lecture: Ø It is the center of the eye's sharpest vision (the greatest visual acuity)and the location of most color perception. 3 Review on previous lecture: Ø It is the center of the eye's sharpest vision (the greatest visual acuity)and the location of most color perception. 4 Review on previous lecture: 5  Review on previous lecture: v The normal cup to disc ratio is about 1/3 or 0.3; 6 v Cup to disc ratio larger than 0.5 is suspicious having glaucoma. Learning Objectives: 7 Learning Objectives: 8 Learning Objectives: RGC BC Phototransduction want light to land in retina light will hit photoreceptor layer photoreceptor receive light stimulation --> convert light signal into electrical signal pass through to visual cortex 9 Learning Objectives: v Visual Phototransduction; v ON, OFF responses of bipolar cells; v The receptive field of RGCs; v Color vision; v Parallel pathways; v Retinol recycle. 10 The retina: photoreceptors 11 The retina: photoreceptors 12 The retina: photoreceptors v Rods deal with low light level and do not mediate color vision; v Humans have a trichromatic visual system; v The three types of cones are L-cones, M-cones and S-cones that respond optimally to long wavelengths (red), medium wavelengths (green), and short wavelengths (blue), respectively; v Visual phototransduction is the photochemical reaction that takes place in photoreceptors. 13 The retina: phototransduction Phototransduction was elucidated by George Wald for which he received the Nobel Prize in 1967. It is so called "Wald's Visual Cycle" after him. George Wald (1906-1997) 14 The retina: phototransduction rod bipolar cells accept signal only from rods cone bipolar cells accept signal only from cones depolarization membrane potential voltage change Hyperpolarization Depolarization Photovoltage is the change in membrane potential induced by a flash, 15 given at time zero. The retina: phototransduction Hyperpolarization Photovoltage is the change in membrane potential induced by a flash, 16 given at time zero. The retina: phototransduction v Visual phototransduction is a process by which light is converted into electrical signals in the rods and cones of the retina of the eye. ion movement v Rod phototransduction is one of the best- characterized G-protein-signaling pathways. There are three players: Ø The receptor is rhodopsin (R); Ø The G protein is transducin (G); Ø The effector is cGMP phosphodiesterase (PDE). 17 The retina: phototransduction rhodopsin & cone opsin are in the outer segment 18 The retina: rhodopsin rhodopson disc vs rhodopsin complexes retinal hide inside (wrapped by?) opsin Rhodopsin is made of opsin and retinal (Vitamin A). 19 The retina: rhodopsin Rhodopsin is made of opsin and retinal (Vitamin A). 20 The retina: rhodopsin 7 transmembrane alpha helices Rhodopsin is made of opsin and retinal (Vitamin A). 21 The retina: rhodopsin-transducin bind to membrane has 3 units Transducin is composed of three subunits: α, β, and γ. 22 The retina: transducin Heterotrimeric G-protein Transducin is composed of three subunits: α, β, and γ. 23 The retina: transducin R* α β γ α ββ γγ GTP phosphorylation GDP GTP GTP (through activated rhopopsin) GTP become activated Transducin is composed of three subunits: α, β, and γ. 24 The retina: photodiesterase(PDE) α γ α β γ α GTP GTP Ø PDE is the key effector enzyme that regulates the level of the second messenger, cGMP. Ø PDE consists of catalytic alpha and beta subunits and two inhibitory gamma subunits that block PDE activity in the dark. gamma on outside: inhibitory unit alpha bind to gamma unit and remove it from a-b 25 The retina: photodiesterase(PDE) α β no gamma: activated cGMP GMP cGMP lead to ion movement 26 The retina: rod phototransduction cyclic GMP gated sodium channel cGMP-gated sodium channels (cyclic nucleotide gated (CNG) channels) to open, need 3 cyclic GMP 27 The retina: rod phototransduction cGMP-gated sodium channels Na+/Ca2+ K+ exchanger (NCKX) -40 mV - -65 mV not affected by light move (esp.) calcium out of the cell located on membrane out segment 28 The retina: rod phototransduction -40 mV “Dark current” inward Na+ current (happens in dark) cycle: maintain constant level of calcium inside the cell 29 how about sodium? sodium-potassium pump from in to out The retina: rod phototransduction v In the dark, a potential difference exists between the inner segments (Positive) and the tips of the outer segments (-ve); v The result is a current flow - this current is carried primarily by Na ions, which enters the outer segment via light sensitive cation channels in the plasma membrane - this is called the dark current; “Dark current” 30 The retina: rod phototransduction v Sodium returns to the inner segment via the cytoplasm of the connecting cilium; v The Na/K-ATPase drives the sodium ion back out and complete the current; v It has been estimated that each rod consumes 5 x 106 ATP molecules rod-1 sec-1 “Dark current” 31 The retina: rod phototransduction Light v Transiently decreases the dark current due to the reduction of Na+ conductance of the outer segment plasma membrane; v This produce a transient hyperpolarisation of the photoreceptor cells (becoming more -ve inside the cells). hyperpolarization “Dark current” 32 The retina: rod phototransduction to reopen calcium channel “Calcium-feedback” mechanisms red dot = Ca2+ 3 cGMP binding to open this channel inactivated activated v GCAP: Guanylyl Cyclase Activating Proteins; 33 v GC: Guanylyl Cyclase. The retina: rod phototransduction 34 The retina: rod phototransduction 35  The retina: rod phototransduction arresting stop phototransduction restore calcium make the cell ready for the next cycle RK: rhodopsin kinase 36 The retina: cone phototransduction (In cones, PDE6c) opsin complex 37 The retina: ON, OFF responses 38  The retina: ON, OFF responses Excitatory Inhibitory Glutamate Glutamate Receptor Receptor In dark Metabotropic: mGluR6 GluR types 39 Ionotropic: AMPA, NMDA The retina: ON, OFF responses 40 The retina: ON, OFF responses ON-center OFF-center 41 The retina: ON, OFF responses 42 The retina: ganglion cells 43 The retina: RGC receptive field 44 The retina: RGC receptive field ON-center OFF-center OFF-surround ON-surround + + 45 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 46 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 47 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 48 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 49 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 50 The retina: RGC receptive field Receptive field structure in ganglion cells: On-center Off-surround 51 The retina: RGC receptive field 52 The retina: RGC receptive field Horizontal Horizontal cells cells "area in which stimulation leads to response of a 53 particular sensory neuron" The retina: lateral inhibition 54 The retina: lateral inhibition 55 The retina: parallel pathways (via glycinergic synapses) (via gap junctions) 56 The retina: parallel pathways 57 The retina: parallel pathways 58 The retina: parallel pathways 59 The retina: cone sensitivity curve 60 The retina: cone sensitivity curve 61 The retina: parallel pathways 62 The retina: parallel pathways 63 The retina: parallel pathways 64 The retina: parallel pathways v Diverse retinal cell types combine the cone signals to create separate red-green, and blue-yellow pathways; v In trichromatic primates, signals from L-, M-, and S-cone types are combined to create red-green and blue-yellow spectrally opponent pathways; v The private-line pathway from a single cone to a midget ganglion cell in the fovea permits the segregation of L- and M-cone signals. 65 The retina: retinol recycle 66 The retina: retinol recycle 67 The retina: retinol recycle Interstitial retinol-binding protein (IRBP) 68 The retina: retinol recycle (retinol dehydrogenase) (lecithin retinol acyltransferase) RPE65 mutation Leber’s Congenital Amaurosis (LCA) 69 The retina: Summary ❀ Trichromatic color vision begins when the image is sampled by S, M and L wavelength-sensitive cone photoreceptors; ❀ Diverse retinal cell types combine the cone signals to create separate red-green, and blue-yellow pathways; ❀ The parvocellular pathway contains sustained responses with good resolution of wavelengths, shapes, and moderate resolution of contrast; ❀ The magnocellular pathway has good temporal resolution and excellent spatial contrast sensitivity. 70 PolyU Any questions? 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