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1、Retinal physiology HCKJSIECRETINAFunction of the retinaTwo major functions it transduces light into neural signals it transmits these signals into a language usable by our visual brainno feedback from our brain to the retina, Retinal neurotransmitters and neuromodulators Intracellular communication
2、Characteristics:Neurotransmitters are synthesised and stored in a presynaptic cellRelease when the presynaptic neuron is stimulatedRegional hyperpolarisation or depolarisation in the postsynaptic neurone, except the ganglion cellRemoved from the synaptic cleft or postsynaptic membrane by degradation
3、 ,or by reuptake into the presynaptic neuroneGABA-aminobutyrate, found in mller cellsSynthesised from glutamic acidGlutamic acid decarboxylase (amacrine cells in mammals)GABA acts as a trophic agent during retinal maturation( decreases while retina maturing)Melatonin N-acetyl-5-methoxytryptamineProd
4、uced by photoreceptors in a circadian fashion (from serotonin )Controlling enzyme is N-acetyl-transferase (denatured by light)Associated with the regulation of photoreceptor disk sheddingMetabolism of melaninRate determing step: conversion of tyrosine to dopaDopa to dopaquinone -non-enzymaticFound i
5、n the posterior pigmented iris epithelium (deprived from the neuroretina)Stable free radicals Retinal metabolismRespiratory rate of the retina is twice that of the brainNot require insulin for glaucose to enter into the cellsGlycolysis occurs even oxygen is enough (lactate accumulation )Mller cells
6、-glucose-6-phospatase GlycolysisGlucose converted to pyruvate and lactate2 ATP sRate determining anzyme : phosphofructokinaseOccurred in the cytoplasmThe Krebs citric acid cycleOxygen dependent 36 ATPsTwo hydrogen released three ATPs Inner mitochondrial membrane TransductionConsists of subunitsBinds
7、 to the intracellular loops of metarhodopsin Phosphodiesterase (PDE)consists of 2units cGMP keeps the ion channels in the rod outer segment membrane openIPM and IRBPIPM: proteins,glycoproteins,GACs,proteoglycanFunctions including retinal attachment and adhesion,molecular trafficking, facilitation of
8、 phagocytosis and photoreceptor outer segment alignment IRBP accounts for 70% of the soluable protein in the IPMProduced by photoreceptors (mainly by cones)Other binding proteins such as cellular retinoid binding proteins and cellular fatty acid binding proteins Properties of photoreceptorsDerived f
9、rom ciliated ependymal cells of the neuroectoderm Most cone lamellae are continuous with the extracellular spaceAbout 1000 lamellae are present in the rod outer segment Disk morphogenesisPlate formation cytoplasm-filled platesExpansion-the plates expand to reach the width of the rod or cone outer se
10、gmentsRim proteinsare added at the cilium and loop outwards into the plasma membraneZipping up of upper and lower membranes (only in rods)Maturation and stabilisation of the disksShedding and phagocytosis of photoreceptor outer segmentsMaximal time: rods(1 hour after light exposure) cones(2-3 hours
11、after darkness)Mammalian rod outer segment disk shedding : light entrained; free running circadian rhythmRPE cells: special receptors for rod out segments; lysosomal acid hydrolases Visual Cycle11-cis-retinal all-trans bathorhodopsin lumirhodopsin metarhodopsin I II IIIAll-trans-retinal retinol IRBP
12、 RPE all-trans-retinyl ester 11-cis-retinol retinalFig. 1. A schematic view of the rhodopsin molecule with each of its amino acids designated as a small circle; the filled circles indicate amino acids that are identical in different species (i.e., conserved by evolution). The seven segments that are
13、 hydrophobic and incorporated into the lipid membranes of the rod discs are also evident, as are the cytoplasmic and intradiscal ends of the molecule. The 11-cis retinal group and its binding to a lysine in the membrane segment of the molecule is also included. A flow chart of the phototransduction
14、cascade in which quantal excitation of rhodopsin leads to activation of the phosphodiesterase (PDE), decreasing cyclic guanosine monophosphate (cGMP) levels, closing of Na+ /Ca+ + channels, and hyperpolarization of the rod. Darkness causes the opposite changes, driven by the feedback inactivation mechanism SUMMARY :The RetinaNeurotransmitters & modulatorsMajor one is glutamateGABA & Glycine Ach, Dopamine, and catechol.Melatonin - photoreceptorsRetinal MetabolismRespiratory rate twice that of brainIns
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