Overview
Vision begins with light in the 400 to 750 nm band of the electromagnetic spectrum being focused by the cornea and lens onto the retina, transduced by rods and cones into graded electrical signals, processed by the retinal middle layer, and carried by ganglion cell axons through the retina-geniculate-cortex pathway to the primary visual cortex and on into dorsal and ventral processing streams. The lecture works through the optical apparatus of the eye and its disorders (glaucoma, refractive error, presbyopia), eye movements, the anatomy of the visual pathway and the characteristic field defect produced by a lesion at each point along it, the cellular machinery of phototransduction and colour vision, dark adaptation, and finally cortical processing and the failures of integration that follow cortical lesions.
The stimulus and the optical apparatus
- The stimuli transduced by the visual system are electromagnetic wavelengths of roughly 400 nm (violet) to 750 nm (red), a narrow band of a spectrum running from radio waves through microwaves, visible light, ultraviolet, X-rays and gamma rays.
- Sclera and cornea: tough connective tissue continuous with dura. The visible sclera is the “white of the eye”, covered by the conjunctiva membrane. The cornea is transparent and is responsible for two thirds of the eye’s total refraction.
- Ciliary body and iris: the ciliary muscle controls lens shape (accommodation for near vision); the iris defines pupil diameter (light reflex); the ciliary body secretes aqueous humor, which flows through the anterior chamber and drains at the angle.
- Choroid: the equivalent of the brain’s pia and arachnoid, continuous with ciliary body and iris. It supplies blood to the deep receptor cell layer of the retina. The retina relies completely on oxidative metabolism.
- Structures of the eye in cross-section: cornea, aqueous humor, pupil, iris, lens, zonular fibers, ciliary muscle, vitreous humor, retina, choroid, sclera, fovea centralis, optic nerve.
Warning
On the sclera and cornea slide the words “conjunctiva” and “refraction” are rendered overlapping or garbled, likely a text-box layering artefact, and were transcribed as best legible.
The retina: structure and blood supply
- Layers of the retina, in the order light meets them: ganglion axons, ganglion cell layer, bipolar cell layer, receptor layer, and pigmented epithelium at the rear.
- Light therefore penetrates past the ganglion, bipolar and other cells before transduction by rods and cones. The pigment epithelium behind the receptors absorbs stray light.
- Blood supply is dual. The middle and superficial layers are supplied by the central retinal artery, which enters via the optic disc. The deep receptor layer is supplied by the choroid. There are no blood vessels at the fovea, which relies on diffusion of O2 and glucose from the choroid.
- Clinical examination of the retina is ophthalmoscopy. The fundus view shows the fovea, macula and optic disc.
- Characteristic retinal appearances on ophthalmoscopy:
- Glaucoma: damage from raised intraocular pressure.
- Diabetes mellitus: increased vascularisation.
- Papilloedema: bulging of the optic disc in raised intracranial pressure.
Focusing, accommodation and refractive error
- Images formed on the retina are upside down and reduced. Most focusing is done by the cornea; the lens adjusts focus by accommodation, driven by the ciliary body.
- Mechanics of accommodation: the contraction state of the ciliary muscle determines the tension the zonular fibers exert on the lens. Contracted ciliary muscle gives lower zonular tension and a more rounded lens; relaxed ciliary muscle gives higher tension and a flatter lens.
- Near vision sequence: increased firing of parasympathetic nerves to the ciliary muscle, contraction of the ciliary muscle, relaxation of the zonular fibers, relaxation of the lens so that it becomes more spherical, near objects brought into focus.
- Distant objects are in focus with ciliary muscles relaxed, zonular fibers under tension and the lens flattened, because rays from a distant object are nearly parallel. Without accommodation, diverging rays from a near object focus behind the retina and the image is out of focus.
- Presbyopia: with age the lens stiffens and is less able to accommodate.
- Corrective glasses and contact lenses alter the location of image focus to correct problems of eyeball length, corneal asymmetry, or decreased elasticity of the lens.
- Nearsighted: eyeball too long, focus falls short of the retina; corrected with a concave lens.
- Farsighted: eyeball too short, focus falls behind the retina; corrected with a convex lens.
Glaucoma
- Development: the drainage canal for aqueous humour becomes blocked, or extra aqueous humor is produced, resulting in increasing eye pressure. That increased pressure damages the blood vessels and the optic nerve.
- There is a characteristic pattern of visual field loss, a scotoma, which progressively encroaches on the visual scene.
- On fundoscopy the rim of the optic nerve becomes thinner as the disc caves in and becomes more cupped, and progressive cupping tracks the progressive field loss.
Eye movements
- Six extraocular muscles control eye movement, innervated by cranial nerves III, IV and VI.
- Mnemonic LR6(SO4)3: lateral rectus is CN VI, superior oblique is CN IV, all other extraocular muscles are CN III.
- Conjugate gaze: both eyes rotate in the same direction. Convergence: both eyes rotate toward the nose.
- Squint or strabismus produces diplopia.
- Types of movement: saccades (rapid jumps that alter fixation), smooth pursuit (fixating on a moving target), and microsaccades at rest.
Visual fields and the retina-geniculate-cortex pathway
- Each eye’s field divides into a nasal hemifield and a temporal hemifield, imaged respectively on the temporal and nasal hemiretina, with a blind spot at the optic disc. Fields are charted on a polar plot with rings at 30, 60 and 90 degrees eccentricity.
- The main pathway runs: retina, optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, optic radiation, visual cortex. Collateral projections go to the pulvinar nucleus and superior colliculus.
Field defects by lesion site
| Lesion site | Defect |
|---|---|
| Optic nerve (complete) | One eye blind |
| Optic nerve (partial) | Unilateral nasal hemianopia |
| Optic chiasm | Bitemporal hemianopia |
| Optic tract | Homonymous hemianopia |
| Optic radiation, complete | Complete homonymous hemianopia |
| Optic radiation, anterior (Meyer’s) loop | Upper quadrantanopia |
| Optic radiation, dorsal fibres | Lower quadrantanopia |
| Visual cortex, bilateral complete | ”Cortical” blindness |
| Visual cortex, unilateral partial (calcarine) | Quadrantanopia or hemianopia with macula sparing |
- Causes illustrated: an internal carotid artery aneurysm for a partial optic nerve lesion, and a pituitary tumour compressing the chiasm from below for bitemporal hemianopia.
- The optic radiation is also called the geniculostriate tract.
Other pathways from the retina
- Retino-hypothalamic tract: special ganglion cells responding to light over a large area of retina project to the suprachiasmatic nucleus of the hypothalamus, the pacemaker for circadian rhythms, which entrains the clock to the day-night cycle. From there to the pineal gland, which secretes melatonin and coordinates rhythms through the body.
- Superior colliculus / pulvinar: optic tract to superior colliculus to pulvinar (and on to visual cortex). Role in unconscious automatic control of orientation to visual stimuli.
- Pupillary light reflex: bilateral; causes the pupil to dilate in the dark and constrict in light. Pathway: light-detecting ganglion cells, to pre-tectal nuclei on BOTH sides, to the Edinger-Westphal nucleus (parasympathetic pre-ganglionic neurons), to the 3rd cranial nerve, to the ciliary ganglion, then post-ganglionic fibres innervating the iris sphincter muscle.
- Light in one eye should constrict both eyes, giving a direct response (illuminated eye) and an indirect or consensual response (contralateral eye).
Important
Raised intracranial pressure puts pressure on CN III and produces a dilated pupil.
Photoreceptors
- Two types of light-sensitive receptor:
- Rods: rod-shaped, highly sensitive, operate at night, grey-scale vision. Roughly 100 million.
- Cones: cone-shaped, less sensitive, operate in high light, colour vision. Roughly 8 million.
- Distribution: cone density is highest at the macula and maximal at the fovea, which contains only densely packed cones, so acuity and colour vision are best there. Rod density peaks outside the fovea. Both fall to zero at the optic disc.
- Ultrastructure: the photosensitive molecule is retinal, which isomerises when struck by light. Retinal is a component of specialised membrane proteins, the opsins. To maximise opsin concentration, rods and cones have massively enlarged membrane surface area formed into discs. The receptor has an outer segment (discs, plasma membrane, membrane folding), a cilium, an inner segment with mitochondria and nucleus, and a synaptic terminal. Rod discs are free floating; cone discs arise from folding of the plasma membrane.
Opsins and colour vision
- Rods contain rhodopsin, sensitive to a broad spectrum of wavelengths, with peak absorbance around 498 nm.
- Cones have three different opsins with different but overlapping (not exclusive) wavelength sensitivities: short-wave 437 nm, middle-wave 533 nm, long-wave 564 nm.
- The relative amount of activity in these three channels generates all perceived colours.
- Colour blindness: affects up to about 10% of males and under 1% of females. It results from abnormal functioning of one or more cone systems and is usually congenital. The most common forms affect the middle or long wavelength sensitive cone systems, causing difficulty discriminating reds, yellows and greens from one another, collectively called “red-green colour blindness”. Tested with Ishihara colour plates.
Warning
On the full-page Ishihara plate slide, faint underlying page text shows through the scanned image and the embedded number is not clearly legible.
Phototransduction
Cascade steps as given on the slide:
- Light energy (photons) isomerises retinal to its all-trans form, releasing and activating opsin.
- Freed opsin acts enzymatically to catalyse activation of the G protein transducin.
- Transducin catalyses activation of the enzyme phosphodiesterase (PDE).
- Activated PDE detaches cGMP from the sodium channels by hydrolysing it to GMP.
- With their ligand cGMP detached, the sodium channels close, preventing Na+ entry and causing hyperpolarisation, which prevents neurotransmitter release at the synapses with bipolar cells.
Summarised as the mechanism of transduction:
- In the dark a specific ion channel is open and allows influx of Na+, the “dark current”. Receptor cells are relatively depolarised and tonically release glutamate.
- Light, a single photon being sufficient, closes this channel. The receptor cell hyperpolarises (transmembrane potential moves from about -40 mV to about -70 mV) and releases less glutamate.
- The reduction in glutamate reduces excitation in some postsynaptic cells but increases excitation in others. Outputs from photoreceptors therefore have varying effects on linking cells, and the net influence of these determines ganglion cell activity.
- Signal chain notation: light, R, R*, T, T*, PDE, PDE*, cascade, cGMP to 5’-GMP.
Retinal middle layer and ganglion cells
- Middle layer contains neurons that link laterally across the retina (horizontal and amacrine cells) and neurons that link receptor cells with output cells (bipolar cells). This is the first stage of processing of visual information and it determines the receptive field properties of the output ganglion cells.
- Ganglion cells are the output neurons of the retina. They receive input from many bipolar and amacrine cells and are therefore influenced by light falling over a certain portion of the retina, the “receptive field”. Their axons enter the optic nerve at the optic disc.
- Two main types carry different kinds of information: M (magnocellular) and P (parvocellular). These are the origin of separate M and P pathways extending right through to the visual cortex, and the LGN is organised into six layers with ipsilateral and contralateral input feeding the M and P channels.
- Special light-sensitive ganglion cells form the origin of the pupillary light reflex pathway.
Dark adaptation
Multiple mechanisms operate to enable vision on moving from daylight to low light:
- Dilatation of the pupils via the pupillary light reflex pathway; fast. Maximum dilatation (8 mm pupil in the dark, versus 2 mm in bright illumination) increases sensitivity 16-fold compared with maximum constriction.
- Reduced influence of the inhibitory parts of ganglion cell receptive fields; fast; increases cell responses to light; mediated by changed activity in amacrine cells.
- Regeneration of rhodopsin in rods; slow, about 30 minutes; gives a 100,000-fold increase in sensitivity. Rods are most sensitive to low light levels. In daylight most rhodopsin molecules are in the converted (bleached) state and unresponsive to any additional light.
Cone and rod dark-adaptation thresholds follow separate curves over time in the dark.
Visual cortex and higher processing
- Retinotopic organisation: the left visual field maps onto contralateral cortex around the calcarine sulcus, with the cuneus gyrus above and the lingual gyrus below, bounded by the parieto-occipital sulcus. The field map divides into a binocular portion, a monocular portion and the macula, each mapping to a defined cortical region.
- Layered structure of primary visual cortex: layers I, II/III, IVA, IVB, IVCα, IVCβ, V and VI, with blobs for colour processing. Layers have different input and output connections and functions. M and P channels from the LGN enter at layer IV; outputs go to secondary visual areas (V2 onwards) and back to the LGN.
- Components of visual perception are further processed by secondary areas in two streams:
- Dorsal stream, the “where” channel: location, depth, motion. Parietal strokes cause neglect.
- Ventral stream, the “what” channel: colour, form, object recognition. Ventral temporal strokes cause prosopagnosia.
- Processing sequence: retina, LGB, primary visual cortex (parvocellular and magnocellular), V2 (thick stripe, thin stripe, interstripe, interblob), then V4/PIT/CIT/AIT ventrally and MT/MST/LIP/VIP/7a dorsally.
- Final integration of visual experience: there is no single “centre” for integrated conscious experience; it arises from interaction between brain structures performing specific processing functions. Lesions disconnecting visual cortex from other regions can therefore affect integration of visual information with movement control, with emotion, or with memory, possibly through loss of connections with the amygdala, which is important for assigning emotional context. Capgras’ syndrome is an example: patients have an integrated sensory experience but believe some acquaintances are imposters.
Lecture checklist
Structures. Eye movements. Focusing abnormalities. Pupil responses. Glaucoma. Retinopathy. Visual fields. Visual pathways and defects. Cortical and processing abnormalities.
Self-test
- State the wavelength range of the stimuli transduced by the visual system.
- Explain which structure performs most of the eye’s refraction and give its share of the total.
- Describe the blood supply of the retina, and explain why the fovea is a special case.
- Describe the sequence of events by which a near object is brought into focus.
- Explain why presbyopia develops with age and which part of accommodation fails.
- Distinguish nearsightedness from farsightedness in terms of eyeball length, where the image focuses, and the corrective lens used.
- Describe the two-step mechanism by which glaucoma damages the eye, and the two changes it produces on ophthalmoscopy and perimetry.
- List the three retinal appearances given for glaucoma, diabetes mellitus and papilloedema.
- State the mnemonic for extraocular muscle innervation and expand it.
- Distinguish conjugate gaze from convergence.
- List the retinal layers in the order light passes through them, and explain what the pigment epithelium does.
- Name the stations of the retina-geniculate-cortex pathway in order.
- A patient has bitemporal hemianopia. Where is the lesion, and what pathology was shown as a cause?
- Distinguish the field defect of an optic tract lesion from that of a complete optic nerve lesion.
- Predict the field defect from a lesion of the anterior (Meyer’s) loop of the optic radiation, and from a lesion of the dorsal fibres.
- Explain what distinguishes a unilateral calcarine cortex lesion from a complete optic tract lesion on field testing.
- Describe the retino-hypothalamic tract and what it controls.
- Describe the pupillary light reflex pathway from photoreceptive ganglion cell to iris, and explain why light in one eye constricts both.
- Explain why raised intracranial pressure can produce a dilated pupil.
- Distinguish rods from cones on shape, sensitivity, operating light level, colour vision and number.
- Explain why visual acuity and colour vision are best at the fovea.
- Describe the five steps of the phototransduction cascade.
- Explain what the “dark current” is and what happens to photoreceptor membrane potential and glutamate release when light strikes.
- Explain why reduced glutamate release from photoreceptors does not simply reduce the activity of all downstream cells.
- Name the peak absorbance wavelengths of the rod pigment and the three cone opsins, and explain how all perceived colours are generated.
- Describe red-green colour blindness: prevalence, cause and which colours are hard to discriminate.
- Name the cell types of the retinal middle layer and state what this layer determines.
- Define a ganglion cell receptive field and distinguish M from P ganglion cells.
- List the three mechanisms of dark adaptation with their speed and the gain in sensitivity each provides.
- Distinguish the dorsal and ventral cortical streams by function and by the deficit produced when each is damaged.
- Explain why there is no single centre for integrated conscious visual experience, and use Capgras’ syndrome to illustrate the consequence of disconnection.
- Integrative: trace a single photon’s signal from the moment it strikes retinal in a foveal cone to conscious recognition of a face, naming the molecular, cellular, pathway and cortical steps involved.
Answers
Reveal answers
- Roughly 400 nm (violet) to 750 nm (red).
- The cornea, which is responsible for two thirds of the eye’s total refraction.
- The middle and superficial layers are supplied by the central retinal artery entering at the optic disc; the deep receptor layer is supplied by the choroid. The fovea has no blood vessels and relies on diffusion of O2 and glucose from the choroid.
- Increased firing of parasympathetic nerves to the ciliary muscle, contraction of the ciliary muscle, relaxation of the zonular fibers, relaxation of the lens so it becomes more spherical, near object brought into focus.
- With age the lens stiffens and so is less able to round up when zonular tension falls, meaning accommodation for near vision is lost.
- Nearsighted: eyeball too long, image focuses short of the retina, corrected with a concave lens. Farsighted: eyeball too short, image focuses behind the retina, corrected with a convex lens.
- The drainage canal becomes blocked or extra aqueous humor is produced, raising eye pressure; the raised pressure damages the blood vessels and optic nerve. On ophthalmoscopy the optic disc rim thins as the disc caves in and becomes cupped; on field testing there is a characteristic scotoma.
- Glaucoma: damage from raised intraocular pressure with a cupped disc. Diabetes mellitus: increased vascularisation. Papilloedema: bulging of the optic disc, seen in raised intracranial pressure.
- LR6(SO4)3: lateral rectus is supplied by CN VI, superior oblique by CN IV, and all other extraocular muscles by CN III.
- Conjugate gaze is both eyes rotating in the same direction; convergence is both eyes rotating toward the nose.
- Ganglion axons, ganglion cell layer, bipolar cell layer, receptor layer, pigmented epithelium. The pigment epithelium absorbs stray light.
- Retina, optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, optic radiation, visual cortex.
- At the optic chiasm. A pituitary tumour compressing the chiasm from below was shown as a cause.
- An optic tract lesion gives homonymous hemianopia, that is loss of the same side of the field in both eyes; a complete optic nerve lesion blinds one eye entirely.
- Anterior (Meyer’s) loop lesion gives an upper quadrantanopia; a dorsal fibre lesion gives a lower quadrantanopia.
- A unilateral partial calcarine lesion produces a quadrantanopia or hemianopia with macula sparing, whereas an optic tract lesion gives a complete homonymous hemianopia without sparing.
- Special ganglion cells responding to light over a large area of retina project to the suprachiasmatic nucleus of the hypothalamus, the circadian pacemaker, which entrains the clock to the day-night cycle and drives the pineal gland to secrete melatonin, coordinating rhythms through the body.
- Light-detecting ganglion cells project to the pre-tectal nuclei on both sides, then to the Edinger-Westphal nucleus (parasympathetic pre-ganglionic neurons), then via the 3rd cranial nerve to the ciliary ganglion, whose post-ganglionic fibres innervate the iris sphincter muscle. Because the pre-tectal projection is bilateral, illuminating one eye constricts both, giving a direct response in the lit eye and an indirect response in the contralateral eye.
- Raised intracranial pressure puts pressure on CN III, which carries the parasympathetic fibres to the iris sphincter, so the pupil dilates.
- Rods: rod-shaped, highly sensitive, operate at night, grey-scale vision, about 100 million. Cones: cone-shaped, less sensitive, operate in high light, colour vision, about 8 million.
- Cone density is highest at the macula and maximal at the fovea, a region containing only densely packed cones, and cones mediate colour vision, so acuity and colour discrimination are best there.
- (1) Photons isomerise retinal to all-trans, releasing and activating opsin. (2) Freed opsin catalyses activation of the G protein transducin. (3) Transducin catalyses activation of phosphodiesterase. (4) Activated PDE hydrolyses cGMP to GMP, detaching it from the sodium channels. (5) Without their cGMP ligand the sodium channels close, Na+ entry stops and the cell hyperpolarises, preventing neurotransmitter release at bipolar cell synapses.
- In the dark a specific ion channel is open and Na+ flows in, the dark current, keeping the receptor relatively depolarised and tonically releasing glutamate. Light, even a single photon, closes the channel, so the cell hyperpolarises from about -40 mV to about -70 mV and releases less glutamate.
- Because reduced glutamate reduces excitation in some postsynaptic cells but increases excitation in others, so photoreceptor output has varying effects on the linking cells, and it is the net influence of these that determines ganglion cell activity.
- Rod rhodopsin peaks at 498 nm; short-wave cone at 437 nm, middle-wave at 533 nm, long-wave at 564 nm. Sensitivities overlap rather than being exclusive, and the relative amount of activity across the three cone channels generates all perceived colours.
- It affects up to about 10% of males and under 1% of females, usually congenital, and results from abnormal functioning of one or more cone systems, most commonly the middle or long wavelength system, causing difficulty discriminating reds, yellows and greens from one another.
- Horizontal and amacrine cells, which link laterally across the retina, and bipolar cells, which link receptor cells to output cells. It performs first stage processing and determines the receptive field properties of the ganglion cells.
- A receptive field is the portion of retina over which light falling influences a given ganglion cell, arising because each ganglion cell receives input from many bipolar and amacrine cells. M is magnocellular and P is parvocellular; they carry different kinds of information and are the origin of separate M and P pathways running to the visual cortex.
- (1) Pupil dilatation via the pupillary light reflex pathway; fast; maximum dilatation increases sensitivity 16-fold over maximum constriction. (2) Reduced influence of the inhibitory parts of ganglion cell receptive fields, mediated by changed amacrine cell activity; fast; increases cell responses to light. (3) Regeneration of rhodopsin in rods; slow, about 30 minutes; 100,000-fold increase in sensitivity.
- Dorsal is the “where” channel handling location, depth and motion; parietal strokes cause neglect. Ventral is the “what” channel handling colour, form and object recognition; ventral temporal strokes cause prosopagnosia.
- Integrated conscious experience arises from interaction between brain structures each performing a specific processing function rather than from one centre, so lesions that disconnect visual cortex from other regions disturb integration of vision with movement control, emotion or memory. In Capgras’ syndrome, possibly from loss of connections with the amygdala which assigns emotional context, the patient has an integrated sensory experience yet believes acquaintances are imposters.
- The photon isomerises retinal to all-trans within a cone opsin, activating opsin, then transducin, then PDE, which hydrolyses cGMP so the sodium channels close, the dark current stops and the cone hyperpolarises and reduces its tonic glutamate release. That change is processed by bipolar cells with lateral input from horizontal and amacrine cells, shaping the receptive field of a P-type ganglion cell whose axon leaves at the optic disc. The axon runs in the optic nerve, decussates or not at the chiasm according to nasal or temporal hemiretina, continues in the optic tract to the parvocellular layers of the lateral geniculate nucleus, then through the optic radiation to layer IVCβ of primary visual cortex around the calcarine sulcus. From V1 the signal passes to V2 and onward through the ventral “what” stream (V4, PIT, CIT, AIT) for colour, form and object recognition, with recognition of a face requiring integration with other regions, notably the amygdala for emotional context, since there is no single centre for conscious visual experience.