Eye and Vision

Fox, a substantial part of Chapter 10

Review

Vision is usually covered everywhere, and Freeman has the topic
TRANSPARENCY (intro book) eye and retina structure
TRANSPARENCY (intro book) spectrum and spectra for the 3 cones that mediate color vision

Eye structure

Fig. 10.27
the eye picture of an ophthalmologist's office
cornea, iris, pupil, conjunctiva, sclera, extraocular muscles
lens, aqueous (anterior chamber), vitreous (vitreous chamber), retina, fovea, optic n.
there is a blind spot where the optic nerve exits

Fig. 10.31
Here is a picture showing focus of an arrow up-side-down on the retina, trivial except that is shows that most of the bending is at the cornea where the change of index of refraction at the air-cornea interface is very large.

Refractive Disorders

Fig. 10.35
refractive errors
diopters - reciprocal of focal distance in m
cornea is 0.024 m, 42 diopters
Emmetropia-normal,
Hyperopia-far-sighted, need convex lens,
Myopia-near-sighted, need concave lens, involves abnormal elongation of the eye
visual angle, acuity - Snellen eye chart - 20/20 is seeing letter 5 min (1/60 degree)

Accomodation and presbyopia

Fig. 10.34
Accomodation
loss of accomodation with age explains Presbyopia
Benjamin Franklin developed bifocals
This is a difficult concept and the best figure I've seen to explain it:
If ciliary muscle is relaxed, ligaments are tight and lens is stretched flat
If ciliary muscle contracts, ligaments have slack and lens relaxes to greater bulge for near vision.

Here, in an albino rabbit eye dissection, you can see the suspensory ligaments of the ciliary muscle.

Other disorders:

Glaucoma - pressure is too high because aqueous humor does not drain well, ganglion cells die, treated with drops or surgery
Floaters in vitreous especially in myopia
Diabetic retinopathy blood vessels overgrow, leak, blast holes in retina with laser decreases angiogenesis
Cataract - lens becomes opaque, remove and often replace with intraocular lens, made of polymethyl methacrylate, known to be tolerated since pieces from airplane visors would nlodge in pilots under fire (and since about 1988, these have been doped with UV blockers)
Retinitis pigmentosa is tragic, people can see when young, lose rod vision (tunnel vision [ring scotoma] because rods are in mid-periphery).
Rods go first and eventually cones which is strange if rod molecules are mutant.
There are autosomal and X-linked types, dominant and recessive.
There are other genetic degenerations and stationary (not progressive) blindnesses are in molecules of transduction cascade (book only mentions missense mutations in opsin) as well as in other rod and cone molecules.
There is a web site where information relevant to the retina, especially genetic causes of blindness, accumulates (site)
Age related macular degeneration may have an genetic basis too

Pupil

Fig. 10.28
An interesting and related story has to do with dilation of the pupil.
Recall that atropine, a muscarinic antagonist, dilates the pupil.
That means that the parasympathetic nervous system constricts the pupil.
Recall that parasympathetic = cranio-sacral, and here the cranial nerve is the occulomotor nerve (#III)
By contrast, the sympathetic n.s. dilates (in dim light), and the nerve has to come up from the superior cervical ganglion (of the thoraco-lumbar system)
A bright light in one eye causes the other pupil to constrict too. (Try this in front of a mirror with a flashlight.)
Neurologists can make use of information based on defects in the pupillary reflex.

Eye structure

Fig. 10.30
"the eye is the window to the brain" -- physician can actually look at CNS
For instance, increased crainial pressure (like from tumor) shows up as papilledema
Optic disc is where optic nerve exits and blood supply enters and exits.
Fovea is high acuity cone vision.
Macula lutea is area where carotenoids (lutein and zeaxanthin) form blue-blocking (yellow) filter.

Here is a picture a friend (Lynette Feeney-Burns) gave me before she retired (in about 1990). It is labeled "normal macular pigment - chow diet," and it demonstrates the density of yellow pigment around the fovea in (presumably) monkeys fed a diet adequate in carotenoids. Currently, it is known that the carotenoids lutein and zeaxanthin are in nerve layers in the light path to the receptors of the fovea (cones). We get these yellow-appearing caroteinois in our diet (e.g. from spinach and corn). It is thought that they help to protect cones from damage that may be induced by blue light. It was found that the concentration is increased with dietary increases, and now lutein is included in multi-vitamins.

Here, in a sheep eye dissection, you can see the optic disc. Retina is white, pigment epithelium and choroid are black.

Rods and Cones

TRANSPARENCY (here is a pdf of this transparency)
Hecht, Schlaar and Pirenne (1942) published a study that a human subject can see a light so dim that 6-14 quanta were absorbed over a 500 rod area; that means one rod can "see" one quantum.
Here are some calculations showing how to determine the energy of a photon using Planck's constant (obviously very low).
I also roughly calculate to show that the threshold for audition is comparably low.

Fig. 10.44
Photoreceptors- 125 million receptors 20/1 rods to cones
(converge on 1 million ganglion cells)
Adds to sensitivity of rods and to acuity for cones.

Retinal circuitry

Fig. 10.36
Retina is mounted backwards relative to the path of light
expands on the above figure with retinal wiring diagram:
Straight through: Photoreceptor -> bipolar -> "ganglion" cells (whose axons form the optic nerve)
Horizontal interactions: Horizontal cells and amacrine cells
Pigment epithelium - melanin, vitamin A conversions, and phagocytosis of spent photoreceptor membrane

rods concentrated off-fovea, cones on-fovea
Rod, peripheral vision, dim black and white, sensitive - "scotopic"
Very sensitive - 1 photon
Cone, fovea, color, acuity - "photopic"
Shown in rats, rods are supported by retinal pigment epithelium
RPE: (1) melanin that blocks light reflection
(2) metabolism to provide 11-cis retinal (chromophore ofvisual pigment, rhodopsin)
(3) phagocytosis and recycling of shed rod tips
Cells are postmitotic and the indigestible residue of the phagolysosomal system is lipofuscin, a fluorescent aging pigment, a topic on which I've done research.

Color vision

Fig. 10.42
spectral sensitivity of rods and 3 cone types
confirms Young -Helmholtz trichromatic theory
3 kinds of cone 420 530 560
3 kinds of cone opsins which are evolutionarily related in humans and OW monkeys
green and yellow (middle and long wavelength) cone opsins are near each other on X
(blue cone opsin is on human chromosome 7, rod on chromosome 3)
evolutionary bottleneck hypothesis color vision re-evolves after nocturnal life (where adaptive pressure for cone vision is relaxed) early in mammalian evolution
Red or green color blindness - on X, thus preferentially in males.
Blindnesses were thought to be from altered genes, but numbr of copies in human population is variable, and cross-over accidents can even make chimeric genes.
Female "carriers" should actually be mosaics of color blind vs normal retina because of Mary Lyon X-inactivation hypothesis
superfamily of G-protein-coupled receptors (7 transmembrane domain receptors)

Phototransduction

Fig. 10.39
light causes 11-cis retinal (aldehyde of vitamin A, retinol) to turn to all-trans.
("retinene" - term used in book - is old fashioned)
George Wald 1967 Nobel prize

Fig. 10.40
The alpha subunit of transducin (the name for the G protein) activates cGMP PDE (phosphodiesterase)
Less cGMP (ligand) and channel closes so cell hyperpolarizes since sodium channel closes.

Fig. 10.41
This figure repeats the above point.
Because there are Na+ channels in the outer segment and a Na+-K+ ATPase in the inner segment (where there are lots of mitochondria manufacturing ATP), there is a dark current turned off in the light.
(Also shows how rod cell is a stack of disks with rhodopsin and other transduction molecules)
Transmitter is released in dark - but less when light is on

Wiring

(and processing - my coverage here will be minimal)

10.45
Temporal retina does not cross at optic chiasm but goes to ipsilateral lateral geniculate nucleus (part of the thalamus)
Nasal retina goes to contralateral LGN
At LGN, inputs from 2 eyes does not mix.
Projection to cortex where eye inputs mix for stereopsis, and processing for contrast, moving lines, angles, etc takes place.
Superior colliculus (important for eye movement control)

My interests center around vision, so a visit to the research interests of my home page will offer various topics about vitamin A, ultraviolet light, and Drosophila mutants. The Biology Department recently hired a vertebrate vision specialist, Judith Ogilvie. Dr. Fliesler in SLU's Ophthalmology Department and Dr. Ariel in SLU's Anatomy and Neurobiology Department are some of my fellow wizards in visual science.

Exam questions from 2004 - 2007 relating to this outline


What intracellular ligand, whose function is to open channels, is decreased when light stimulates a rod?

cGMP

Energy equals Planck's constant times the frequency. Energy of what?

of one photon

For what population of people is macular degeneration most common?

elderly

What must be bound to the G-protein-coupled-receptor protein to make the fully-functional rhodopsin molecule that absorbs light?

retinal

What happens to a rod's neurotransmitter release when light hits the rod?

decreases

The ciliary muscle contracts, in accomodation, to let you do what?

see up close

How does an eye care professional test for glaucoma?

poke the eye for a pressure check

In the dark, a current of Na+ ions flows from the sodium pump in the inner segment through what in the outer segment?

channels

When an axon from a ganglion cell goes toward the brain in the optic nerve, where does it first synapse?

thalamus

What layer at the back of the eye is black?

retinal pigment epithelium, also choroid

Some men taking Viagra (sildenafil) report impaired color vision. Why might this be?

Viagra and phototransduction both involve cGMP

Where are the genes of the long- and middle-wavelength cone rhodopsins located?

X chromosome

Our gaze seems more relaxed for far vision even though suspensory ligaments are relaxed for the lens to accomodate for near work. What does contract to change the lens shape to see up close?

ciliary muscle

A current of Na+ in the dark along the rod is from the Na+/K+ pump in the inner segment and what in the outer segment?

Na+ channel (or transduction machinery)

What specific cellular defect explains the tunnel vision (ring scotoma) of retinitis pigmentosa?

rods degenerate

What is the only direct effect of light in initiating phototransduction?

cis -> trans isomerization of retinal

What kind of lens corrects for myopia (near-sightedness)?

concave

Which two rhodopsins used for human color vision are coded by adjacent genes on the X chromosome?

middle and long wavelength (green and red [yellow])

Ganglion cells are killed from high eye pressure. What is this disorder called?

glaucoma

What layer of black cells supports rod outer segments by phagocytosis and conversions of vitamin A?

retinal pigment epithelium

Epinephrine binds one G protein-coupled receptor (GPCR). What other GPCR, used for vision, is a pigment that contains a form of vitamin A?

rhodopsin

As it applies to diabetic retinopathy, what is angiogenesis?

formation of new, fragile, blood vessels

Laser photocoagulation decreases angiogenesis. Here we are treating to prevent further blindness from what disorder?

diabetes

Which side of the retina projects to the ipsilateral lateral geniculate body at the optic chiasm?

temporal

Macular degeneration (MD) aflicts a certain population as reflected by the "A" in the name (AMD). What population?

elderly (A=age-related)

Under what conditions are cGMP levels in the rod lowered?

when stimulated by light

Why is it inaccurate to consider a chromosomally normal woman to be be a carrier for a recessive X-linked color blindness if the other chromosome is normal (wild-type, dominant)?

mosaic of cells with one vs the other X functioning (Mary Lyon X inactivation hypothesis)

Why does each eye have a blind spot?

there can be no receptors where the optic nerve exits

Why is cataract usually a less severe form of blindness than retinitis pigmentosa?

there is straightforward surgery for cataract, whereas rods die and cannot be recovered for rp

Scientific information has led to the decades-old conventional wisdom that vitamin A is good for vision. Other than being the pigmented portion of rhodopsin, where else do carotenoids come in to play, explaining why lutein is a dietary supplement or a component in a multi-vitamin pill?

macular pigments protect fovea from blue light

Presbyopia is a defect in what process that affects most people over 40 years old.

accomodation

Why is the cornea actually a stronger lens in the eye than the lens?

because of the big change in index of refraction from the air-cornea interface

Why is the rod depolarized in the dark (but not in the light)?

because cGMP opens sodium channels

The genes for the yellow- and green-light absorbing rhodopsins are near each other on which chromosome?

X

The tip of the rod outer segment is sloughed off on a daily basis and "recycled." Where does this cellular fragment go?

into retinal pigment epithelium

What does activation of the parasympathetic portion of the occulomotor nerve do to the pupil?

closes

If your eye pressure is high, answer ONE of the following: (1) name of disorder, (2) what is not draining appropriately, or (3) loss of what cells mediates vision loss?

glaucoma, aqueous humor, ganglion cells

How can rhodopsin be mutant yet the patient still can see until retinitis pigmentosa first presents in the teens or 20's?

in autosomal dominant, a normal recessive gene still expresses rhodopsin

Suppose you could stimulate a nerve to achieve the same effect as applying belladonna alkaloids to the eye. What type of nerve would you stimulate?

sympathetic

A whole lot of rods converge onto each ganglion cell. What does this wiring achieve?

sensitivity

What is lost in age related macular degeneration (AMD)? (Your answer can be cellular or functional.)

cones, fovea; vision

If you stare straight at a mark (X), while a stimulus is presented to both eyes to the right of the X, describe how the stimulus projects to the thalamus (lateral beniculate nucleus).

temporal retina of left eye - ipsilateral projection; and nasal retina of right (contralateral) to left

In the molecular mechanism from light absorption to hyperpolarization of the rod, exactly what does 11-cis retinal do?

absorb light, convert to trans

Why would you see much better under water with vs without goggles?

keep the normal air-cornea interface (with the normal indices of refraction)

"The blind spot is about 15o off fovea in your nasal retinal field (temporal visual field)." Translate.

location off axis is measured in angle, since the optic nerve exits 15o on the side toward the nose, the inversion of the image would make it seem 15o off to the side

"Visual experience can influence the progression of myopia." On what basis can that statement be made with scientific authority?

research where the vision was distorted with goggles and the eye changed

"If the ciliary muscle is relaxed, the ligaments are tight and" Finish this thought with respect to the shape of the lens and what that does for vision.

lens flattens for distance vision

In the course a lifetime, a retinal pigment epithelial cell's ability to carry out it's function might deteriorate. Why?

it fills with the indigestibloe residue of the phagolysosomal system

If you were convinced that blue light damages foveal cones, how might you alter your diet starting now, while you are young, to delay age related macular degeneration (AMD)?

eat veggies or vitamin pills with lutein or zeaxanthin

With what sort of methodology were scientists as early as 1942 able to come to the conclusion that a rod can respond to one photon?

psychophysics, human subjects report if they can see calibrated lights

"A derivative of vitamin A is the chromophore of rhodopsin." Translate.

vitamin A aldehyde is the light absorbing portion attached to the protein

Why would the evolution of red-green color vision on the X chromosome relate to the richness of olfactory sensation?

it is a simple example of the evolution of G protein-coupled receptors

"Color normal is dominant, color blind is recessive, hence women can be heterozygous carriers for green blindness." Why is this an oversimplification?

they would be mosaics of cells with one or the other X functioning

Why is there an extracellular current from the rod outer segment to its inner segment in the dark?

The channel letting Na+ in is in the OS, the sodium pump is in the IS

In terms of the channel gating, why does a rod hyperpolarize in response to light?

the ligand (cGMP) that holds the Na+ channel open is broken down



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this page was last revised 8/7/08