Retina (Dr. Najeeb and UCL )

  • Procencephalon divides into Telencephalon and Diancephalon (diana)
  • Outpouching from diancephalon called optic vesicle develops invagination (optic cup).
  • Outer layer of optic cup differenciates into pigmented retina
  • Inner layer of optic cup differenciates into neuronal retina
  • Optic nerve passes through lamina cribrosa and merges with neuronal fibres posteriorly to form optic disc
  • central retinal artery supplies inner part of retina (neural layer)
  • Outer part of retina (RPE) receives blood supply from posterior ciliary artery/choriocapiliaries from choroid.
  • Choriocapillaries are vascular circular sinusoids (capillary loops)

Macula depends on choroidocapiliary diffusion (avascular structure)

  • Retina is divided into two parts: inner neurosensory retina and outer retinal pigment epithelium -→ two layers are adherent due to negative pressure, viscous proteoglycans and electrostatic forces

Surface area of retina: 1250mm2

Retinal Regions

  • Posterior pole (area centralis) : between superior and inferior retinal arcades - a cone rich region with more than one layer of ganglion cells
  • Macula lutea/fovea:
    • Diameter - 1.5mm
    • 3mm lateral to optic disc
    • Rich in xanthophyll carotenoid pigment (UV block)
  • Fovea centralis/foveola
    • Diameter - 0.35mm
    • No rods but maximal cone density
    • Foveal Avascular zone -→ relies on choriocapillaries for nutrition (0.5mm in diameter)
  • Optic disc
    • 3mm medial to macula and corresponds to blind spot (1.8mm)
    • The peripapillary area is thickest region of retina (230um)
  • Peripheral retina - thinnest region of retina (110-140um) and rich in rods
  • Ora serrata - anterior scalloped region of retina, it is 1mm closer to limbus on nasal aspect than temporal aspect of eye

Neuronal Retinal layers

  • Epithelial cells

  • Photoreceptor cells

  • Neuronal Cells

  • Glial Cells

  • RPE Contains melanosomes and are held to each other by tight junctions

  • Rods contain rhodopsin on outer segment which has photoreceptive component. Spherule is synaptic terminal

  • Cods has pedicule synaptic terminal

  • Both rods and cones have photoreceptive part facing towards outer retina and have synaptic terminals facing inner side of retina (towards bipolar cells)

  • Bipolar cells - multiple rods are connected to one bipolar cell but only one bipolar cell connects to one cone (in fovea) - these behave like dendrites

  • Photoreceptor and Bipolar cells have ability to produce graded potentials - these transfer to ganglion cells to produce action potentials

  • Ganglion cells are main output cells which connect to the optic disc - the current of electrical flow is radial (from outer retina to inner retina) flow is RBG

  • Interconnecting cells (HAI cells ) located in plexiform layers (plexiform means connection)

    • Horizontal cells connect between photoreceptors connecting laterally and are found in outer plexiform layer - these are usually inhibitory cells and are mediated by GABA
    • Amacrine cells cross talk between Bipolar and Ganglion cells and connect laterally within the inner plexiform layer are usually GABAminergic but also can release glycine, Dopamine and
    • Inter-plexiform cells connect OPL with IPL and take information in reverse direction (from inner to outer)

  • Rods and Cones use glutamate as neurotransmitter to bipolar cells ==> Bipolar cells also are glutaminergic to connect to ganglion cells== > Ganglion cells are using glutaminergic to connect to optic tract

  • RADIAL CURRENT is GLUTAMINERGIC

  • Glial cells are supportive cells (MAM cells) cells which ensure RBG cells and HAI cells remain intact

    • Muller cells originate between inner/outer plexiform later - they fixate rods and cones together through zona adherens (OUTER LIMITING MEMBRANE) and keep inter-photoreceptor fluid and matrix within the layer so doesnt escape beyond through to internal retina
    • Muller cells have foot plates which are a boundary between retina and vitreous (INNER LIMITING MEMBRANE)
    • Astrocytes support neuronal structures, ganglion layer structures and capillary structures -
    • Microglia are macrophages which are spread throughout retinal layers and remove cellular debris which have broken down

Layers of Retina

  1. RPE - acts as blood-retinal barrier between choroid
  2. Rod/Cone layer
  3. External limiting membrane (muller cell connections)
  4. Outer nuclear layer (nuclear of rods cones)
  5. Outer plexiform layer (supplied by choriocapillaries)
  6. Inner nuclear layer (nuclear of bipolar cells with amacrine cell and horizontal cells)
  7. Inner plexiform layer
  8. Ganglion cell layer
  9. Retinal Nerve Fibre Layer
    1. Inner Limiting Membrane (muller cell foot plates)

RPE

Structure

  • RPE acts as barrier between choriocapillaries and neuro-retina - choriocapillaries give nutrition to outer 5 layers (RPE to outer plexiform layer)

  • Continuous monolayer of hexagonal cuboidal cells (optic nerve head up to ora serrata) -→ 4.2-6.1 million cells

  • More columnar in central retina and more flattened in peripheral retina

  • Each RPE cell is joined to their apical margins by tight belt junctions (zonulae occludentes)

  • In zonular occludentes, plasma membranes are fused and impermeable to water and ions -→ forms outer blood-retinal barrier

  • 45 photoreceptors per RPE cell i nall retinal regions

  • RPE cell loss leads to hyperplasia of adjacent cells as regenerative capacity is low

    Function

  • Vital in vitamin A metabolism and regeneration in visual cycle

  • Absorbs extra light to prevent internal reflection of eyeball to reduce chances of glare and reduced quality -→ albinos do not have melanosomes so find seeing in bright light difficult

  • Regeneration of bleached visual pigment

  • Breaks down older components of outer segments of rod/cones (phagocytosis of outer segment tips

  • Secretion of matrix and Produces growth factors released to choriocapillaries, subretinal space and rod/cones to maintain structure/function

  • Lipofucin granules (which increase with aging) represent outer segment lipids incompletely digested by lysosomal activity -→ the highest density of RPE lipofuscin is found in the macula. This can compromise the RPE and promotes RPE apoptosis and may contribute to AMD.

Rods/Cones

  • Cones (6.5 mill) have iodopsin, Rods have rhodopsin
  • Rods (115 mill - 20:1) at low lumination can give signals/sensitivity as multiple rods are connected to one bipolar cell, sum of their graded potentials allow action potential to fire from ganglion cell -→ responsible for contrast, brightness and motion
  • Cones activate at different wavelengths of light, have 1:1 connection with bipolar cells so can see more detail in better light settings -→ responsible for fine resolution, spatial resolution and colour vision
  • Rods are generally in periphery, Cones are generally in fovea/macula
  • Fovea is point of sharpest visual acuity because
    • Light directly hits cones and bypasses retinal layers
    • Cones > Rods
    • 1:1 cone:bipolar cell ratio

Ganglion cells : some cells have illumination qualities which can send signals independently to hypothalamus (supra-chiasmatic nucleus) via retino-hypothalamic pathway determines circadian rhythm and day/night time

Retinal nerve fibre layer in retina are not myelinated as it is a reflective structure and would cause degradation of the image -→ as soon as RNFL hits optic nerve, there is myelination from oligodendrocytes.

Main visual pathway: Optic nerve -→ optic chiasm -→ lateral geniculate body -→ optic radiations -→ visual cortex

Accodomation/light/pupillary reflex: Optic nerve -→ optic chiasm -→ superior colliculus/pretectal nucleus (degree of illumination of light to midbrain) -→ edinger westphal nucleus -→ parasympathetic fibres to ciliary ganglion -→ ciliaris muscle and sphincter pupillae for light/accomodation reflex

Other pathway: Optic nerve -→ optic chiasm -→ SCN (hypothalamus) -→ control circadian rhythm (with pinneal gland).

Blood Supply

  • Retinal vascular system supplies 5% of oxygen used in fundus, choroid supplied by rest

  • Inner 2/3rds of retina are supplied by central retinal artery

  • Outer 1/3rd is supplied by choroidal vessels

  • Arterial branches have smooth muscle walls, endothelium but lack an internal elastic lamina

  • Central Retinal artery (0.3mm in diameter) arises 1cm behind eye from ophthalmic artery (1st branch of ICA), pierces inferomedial aspect of optic nerve and enters globe via cribiform plate (potential for obstruction) -→ becomes 0.1mm in diameter here

  • Cilioretinal artery arises from posterior ciliary vessels and provides anastamosis between retinal and choroidal circulation

  • Inner plexus retinal artery -→ GCL

    Outer plexus retinal artery -→ INL

  • Retinal capillaries endothelium have non-leaky tight junctions (inner blood retinal barrier) and are densest at the macula

  • Ophthalmic artery and its brnahces are innervated richly with adrenergic fibers until lamina cribrosa is reached -→

Venous supply

  • retinal veins drain inner retinal via four vascular arcades into central retinal vein which drains into cavernous sinus -→ can occasional drain via superior ophthalmic vein
  • Central retinal vein shares common sheath with CRA as they exit globe through lamina cribrosa of optic nerve
  • Retinal veins are posterior to arteries at vessel crossing points