Physiology Of Retina in ophthalmology.pptx

full explanation of physiology of retina.

1. PHYSIOLOGY OF RETINA PRESENTED BY; DR. RAHUL GUPTA 1 st YR RESIDENT DEPT. OPHTHALMOLOGY DATE: 15TH OCT, 2023

2. PRESENTATION LAYOUT Introduction Physiology of the RPE/ Neural Retina Visual Cycle Phototransduction Information processing within the retina Light Adaption

3. INTRODUCTION

4. Light passes through most of the retinal layers Reaches and stimulates the photoreceptor outer segment discs The neural flow then proceeds back through the retinal elements in the opposite direction of the incident light

5. PHYSIOLOGICAL FUNCTION OF THE RPE Absorption of scattered light Blood retinal barrier function Visual pigment regeneration and synthesis Synthesis of growth factors Maintenance of retinal adhesion Phagocytosis Electrical homeostasis Repair and regeneration after injury

6. Absorption of scattered light Retinal pigments

7. MELANIN Contain within the cytoplasmic granules : melanosomes In old age, these pigments fuse with lysosome and break down FUNCTION ; Absorbs stray lights and minimize scatter within the eye. Serves as a free radical stabilizer, bind toxins and retinotoxic drugs.

8. LIPOFUSCIN Accumulates gradually with age Derived from The outer segment lipids that have been ingested and then digested by the RPE Membrane fragments that have been damaged by the light or oxidation Drusen

9. Best’s Macular Dystrophy Extremely rare – AD Bestrophin / VMD2 gene Encodes for transmembrane Cl - channel Accumulation of lipofuscin secondary to abnormal ion flux

10. Stargardt Disease Fundus Flavimaculatus (FFM) AR Diffuse accumulation of lipofuscin within the RPE Gradual impairment of central vision which may be out of proportion to the macular changes

11. Control of fluid and nutrient in the subretinal space RPE constitute a monolayer of cells; cuboidal in cross section and hexagonal when looked from above. Joined by the tight junctions ( zonulae occludens) Block the free passage of water and ions Equivalent to blood retinal barrier which are formed by the capillary endothelium of intrinsic retinal vasculature.

12. Trans Epithelia Transport Transport from blood to photoreceptor side Glucose Omega 3 fatty acid All trans retinol Transport from retinal side to blood side Water Lactic acid

13. Retinal side – Blood Transport of water Transport of lactic acid

14. Growth Factors Functions: Vascular supply Permeability Growth, repair and other processes vital to retinal function Platelet Derived Growth Facto r (PDGF) Modulates cell growth and healing Pigment Epithelium Derived Facto r (PEGF) Neuroprotectant and vascular inhibitor Vascular Endothelial Growth Facto r (VEGF) Stimulate normal or neovascular growth Fibroblast Growth Factor (FGF) Neurotropic Transforming Growth Factor Modulates inflammation

15. APPLIED ANATOMY ARMD( Age related macular degeneration) Degenerative changes in the RPE cells, extracellular matrix and possibly choriocapillaries – malnutrition of photoreceptors and RPE cells ATROHIC FORM NEOVASCULAR FORM Insufficient production of survival factors by damaged RPE Leading to apoptosis of functional complexes formed by choriocapillaries , RPE and photoreceptors RPE and possibly photoreceptors produce excess VEGF Stimulates outgrowth of new capillaries , CNV Occult VS Classic

16. Retinal adhesion Factors keeping the retina attached 1. Mechanical forces outside the sub retinal space: Fluid pressure : Hydrostatic & Osmotic fluid Aqueous is driven from the vitreous towards the choroid, but the posterior route is limited because the retina & RPE provide substantial resistance to water movement. Hence as an effect of this outward push of fluid the retina remains on the wall of the eye.

17. Pressure difference across the retina Vitreous adhesion: the vitreous has a physical structure of a gel that may help to keep the retina in place

18. 2. Forces in the sub retinal space: a. RPE pump : -the RPE can pump fluid out of the subretinal space to the choroid at the rate of 0.3microL\ hr \ sqmm . -this is an active energy dependent process and keeps the subretinal space dry. b. Mechanical interdigitation : -the RPE microvilli wrap closely around the tips of the outer segments of the photoreceptors .

19. c. Inter photoreceptor matrix : Cell-cell adhesion mediated by cell adhesion molecules, which are intrinsic membrane glycoproteins. Cell-matrix adhesion mediated by matrix molecules like fibronectin, laminin, collagen and proteoglycans.

20. Interphotoreceptor Matrix(IPM) and inter Photoreceptor Retinoid Binding Protein (IRBP) IPM Occupies space between Photoreceptor OS and RPE Contains: proteins, glycoprotiens , GAGs and proteoglycans (chondroitin sulfate) Functions: Retinal attachment and adhesion, molecular trafficking Facilitation of phagocytosis

21. IRBP: 70% of soluble proteins in IPM Only binding protein found in retina Produced mainly by cones (PR) Binds all- trans – retinol, 14- cis -retinal, ὰ - tocopherol , retinoic acid and cholesterol Function: Efficient transport of retinoids between PR and RPE Minimize fluctuation of retinoid availability Protect plasma membrane form damaging effect of high concentration of retinoid

22. Phagocytosis Damage Membranes Over time Free Radicles

23. Within the RPE the phagocytosed disc becomes encapsulated in vesicles called phagosomes Merge with lysosome for digestion Fatty acids are retained for recycling into outer segment Waste or damaged membrane material is egested across the basal RPE membrane

24. Electrical homeostasis Selective ion channels and number of active or facilitative transport systems for ions and metabolites such as glucose and amino acids Different channels are present in both apical and basal membranes Movement of water across RPE is in apical to basal direction and the generation of voltage across the RPE. The pump mechanism is very powerful and can pump fluid against a substantial gradient of hydrostatic or osmotic pressure

25. CLINICAL CORRELATION Central serous retinopathy Serous detachment is not that fluid gets in( given that a break is present in RPE barrier) but that the fluid accumulates and persists (since the powerful RPE would be expected to pump it right back)

26. Electrical Activity In RPE Asymmetrical transport property of apical and basal membrane generates transepithelial voltage(standing potential) Light incident upon the photoreceptors causes the potassium concentration of subneural retinal space falls Response: apical membrane of RPE and muller cell hyperpolarizes Light activation of photoreceptors causes the release of unknown messenger subs that causes the basal RPE depolarization.

27. Repair And Regeneration Although of neural origin the RPE are the pluripotent tissues capable of local repair and cell migration. Examples; Laser burns : RPE surrounding the burn begin to divide and fill the defect to form a new BRB within 1-2 weeks. Retinitis pigmentosa : RPE migrate into the injured neural retina and comes to rest around vessels to contribute the characteristic bone spicule appearance Macular degenerative process : vigorous RPE response can lead to duplicated layers of RPE cells and RPE scarring

28. The most important function of RPE is the ability to heal defects Valuable in photocoagulation for macular edema and proliferative diabetic retinopathy The ability of RPE cells to seal laser scars, re-establish a degree of normal transport and avoid unnecessary leakage of proteins into the subretinal space.

29. PHYSIOLOGY OF THE NEURAL RETINA 80 to 110 million rods 4 to 6 million cones Approximately 35 million bipolar cells 1.12 to 2.22 million ganglion cells Signals from numerous photoreceptors converge at one ganglion cell

30. 75,000 rods 5000 rod bipolar cells 250 amacrine cells Single ganglion cell

31. Relatively small number of cones drive the cone bipolar cell Small number of cone bipolar cells drive a single ganglion cell In some situations, 1:1 ratio between cones and ganglion cells Reflecting the significant amount of detail that the cone population can discriminate

32. PHOTORECEPTORS AND VISUAL PIGMENTS Night (scotopic) vision - rod photoreceptors Daylight (photopic) vision - cone photoreceptors Twilight (mesopic) vision - combination of cones and rods

33. Rhodopsin Present in the disc of rod outer segment Consist protein: opsin( scotopsin ) carotenoid( retinal, aldehyde of vitamin A) Membrane bound glycolipid held in rigid , highly organized arrangement coupled to G- protein MW: 40,000 Peak sensitivity lies within narrow limit of 493-505 nm- in chromosome no 7

34. Opsin long helix 348 amino acids Loop seven times Light absorbing form of vitamin A is retinal which bind to opsin at Schiff base linkage to form rhodopsin

35. Cone pigment The protein opsin in L-cone cells : red sensitive 580 nm M-cones : green sensitive 535 nm S-cones : b lue sensitive 435 nm - chromosome 7 Chromosome 10q 435nm 535nm 580nm

36. Pathology Retinitis Pigmentosa Progressive Cone Dystrophy Leber’s Congenital Amaurosis Congenital Stationary Night Blindness Fundus Albipunctatus

37. LIGHT INDUCED CHANGES Photochemical changes studied in rods outer segment is studied in following 3 headings Rhodopsin bleaching Rhodopsin regeneration Visual cycle

38. VISUAL CYCLE VISUAL CYCLE

39. NEUROPHYSIOLOGY OF VISION Genesis of visual impulse in photoreceptors/phototransduction Processing and transmission of visual impulse in retina Processing and transmission of visual impulse in visual pathway Analysis of visual impulse in visual cortex

40. Phototransduction Series of biochemical events that leads from photon capture by a photoreceptor cell to its hyperpolarization and slowing of neurotransmitter release at the synapse. Photon of light is changed to an electrical signal Occurs in the photoreceptors Visual pigments in the photoreceptor outer segment absorb light Initiates the process of vision

41. IN THE DARK STANDING POTENTIAL/ DARK POTENTIAL

42. Photoreceptor depolarized approximately −40 mV membrane potential Voltage-gated Ca ++ channels open Calcium ions facilitate glutamate release into the synaptic cleft In the dark, photoreceptor terminal continuously release glutamate

43. IN LIGHT

44. Photoreceptor cells Depolarized in the dark Light hyperpolarizes and switches off these cells This 'switching off' that activates the next cell and sends the signal down the neural pathway depending on the type of cells

45. Incident Light Change in Opsin Configuration Retinene 1 changed to All-trans form α -Subunit separates Transducin (G α) is activated Subunit activates cGMP PDE

46. Reduced cytoplasmic cGMP Hyperpolarization≈ -70 mV Converts cGMP to 5 ’ -GMP Closure of leaky Na + Channels “Switching off”

47. Decrease intracellular Ca 2+ Electrical signal down the neural pathway Decrease Glutamate release Depolarization (rod and cone On Center bipolar cells) Hyperpolarization (cone Off surround bipolar cells)

48. Light Photoreceptor Hyperpolarisation Dark Photoreceptor Depolarisation Decreased Glutamate release Increase Glutamate release ON bipolar : Depolarise OFF bipolar: Hyperpolarise OFF bipolar: Depolarizes ON bipolar : Hyperpolarise

49. Bipolar Cells First cells in the visual pathway to respond with an action potential Once a threshold is reached, the ganglion cell responds and a signal is sent to higher CNS locations Rod bipolars do not synapse with ganglion cells directly but with amacrine cells

50. When Glutamate binds to the ionotropic receptor on a bipolar dendrite Cation channels are opened in the cell membrane, causing the bipolar cell to depolarize and release Glutamate This is an OFF bipolar because it is depolarized in the dark/hyperpolarize in light

51. When Glutamate binds to the metalotropic receptors on a bipolar cell dendrite Decrease of cGMP occurs Closing cation channels in the cell membrane and causing the bipolar cell to hyperpolarize Results in a decrease of glutamate release This is an ON bipolar because it is hyperpolarized in the dark/ depolarized in the light

52. Amacrine Cells Receive information at the synapse of the bipolar cell axons with the ganglion cell dendrites Bipolar cells project onto both ganglion and amacrine cells Negative feedback Reciprocal inhibition

53. Horizontal cells Antagonistic interneurons that inhibit photoreceptors by releasing GABA when depolarized Dendrites of horizontal cells go to cones. One class goes to L and M cones and another class goes to S cones Axon from cell body of horizontal cell send dendrites to rods Dendrites of horizontal cells receive glutamate from rods and cones and release GABA back to cones and rods-provides negative feedback When light causes the cones to hyperpolarize and stop its transmitter release horizontal cell is also hyperpolarized(turned off) – stops the release of GABA from horizontal cell on to cone and thus depolarize the cone

54. Ganglion Cell Electrical response of bipolar cells after modification by the amacrine cells Transmit the information by means of action potential Two types depending upon their response upon illumination of the centre of receptive on center : increase their discharge off center: decrease therir discharge Three groups :W, X And Y ganglions

55. Muller cells: Play a supportive role to the neural tissue extending from inner segments of photoreceptors to inner limiting membrane Buffer the ionic concentration in extracellular space seal off subretinal space by forming the ELM Plays a role in Vit A metabolism of cones

56. INFORMATION PROCESSING RECEPTIVE FIELDS Consists of the area in the visual field or the area of the retina that, when stimulated, elicits a response in a retinal neuron All the photoreceptors and horizontal cells can influence it Receptive field is enlarged beyond its dendritic tree

57. Receptive Fields.... When light activates cells in the center field , a given response occurs When light falls on the surround , an antagonistic response occurs Arranged in a center-surround pattern

58. The center-surround response occurs in part due to Lateral inhibition by horizontal cells Amacrine cell activity on bipolar axon terminal

59. The center-surround configuration allows a neuron To respond to a direct message To gather information from neighboring areas Provide details e.g. detection of edges Maximizes retinal contrast sensitivity

60. VISUAL ADAPTATION LIGHT ADAPTATION Ability of the visual system to adjust its performance to the ambient level of illumination is known as “light adaptation”. occurs very rapidly (within seconds), whether the light intensity is increasing or decreasing.

61. DARK ADAPTATION Ability of the eye to adapt itself to decreasing illumination Dark adaptation occurs slowly, and full recovery of the scotopic visual system after a very large bleach can take as much as an hour. When one goes from bright sunshine into a dimly-lit room, one cannot perceive the objects in the room until some time has elapsed During this period, eye is adapting to low illumination

62. Dark adaptation curve Visual threshold falls progressively Initial small curve represents the adaptation of cones Remainder of the curve represents adaptation of rods

63. 1 minute : 10 x sensitivite 20 minute : 6000 x sensitive 40 minute : 25000 x sensitive When fully dark adapted, the retina is about one lakh times more sensitive to light than when bleached

64. Mechanism Visual pigment mechanism Other mechanisms; - Change in pupil size - Neural adaptation

65. Factors prolonging the dark adaptation Vitamin A deficiency Anoxia Tobacco Anaesthesia Opacities in the ocular media Retinal degeneration Myopia