MAU
THE EYE
AQUEOUS HUMOR
Anterior Chamber Bathes the interior of the cornea (tears bathe the exterior) Isoosmotic fluid that contains:
Salts Albumin Globulin Glucose Other constituents
VITREOUS HUMOR Gelatinous mass that helps maintain the shape of the eye while allowing it to remain somewhat pliable.
THE CORNEA
ABSDE
CORNEA
Clear tissue, diffracts light (like lens), no blood vessels Permeable to water and oxygen
To maintain clarity Has a water pump, uses ATP from TC and CHO metabolism
CORNEA
Corneal stroma water content must be controlled to maintain clarity (ATPdriven water pump) Clearness due to: 1. arrangement of collagen molecules of the stroma. 2. lack of blood vesicles in the epithelial layer (due to VEGFR-3)
Prevents growth of blood vessels by: 1. binding to growth factors or; 2. neutralizing growth factors that are produced to stimulate blood vessel growth.
CORNEA
Obtains its ATP from Aerobic Glucose Metabolism: Glycolysis and TCA cycle. Lactate does not accumulate due to efficient use of Pyruvate (oxidative metabolism) and presence of water and oxygen. Glucose metabolism 30% - glycolysis 65% - hexose monophosphate pathway
CORNEA
Highest activity of HMS (PPP) of any mammalian tissue. High activity of GLUTATHIONE REDUCTASE that requires NADPH (product of HMS)
CORNEA
Corneal Epithelium is permeable to atmospheric oxygen. Reactions to oxygen can lead to formation of various ACTIVE OXYGEN SPECIES that are harmful to tissues by: 1. Oxidizing protein sulfhydryl groups to disulfides 2. Lipid Peroxidation, mostly of cellular medium chain lipids of six carbons or more.
CORNEA
Reduced glutathione (GSH) reduces disulfide bonds and lipid peroxidases (back to original native states) GSSG (oxidized glutathione) formed by: 1. GSH itself 2. Active oxygen species (directly)
CORNEA
Glutathione Reductase uses NADPH to reduce GSSG to 2GSH.
CORNEA
The pentose phosphate pathway and glutathione reductase help protect the cornea (neutralizing active oxygen species) from oxygenation along with oxygen and water permeability
CORNEA
Some lipids that are subjected to peroxidation may spontaneously form active aldehydes that react with other tissue components and lead to various pathological conditions.
CORNEA
The cornea also contains an Isoform of ALDEHYDE DEHYDROGENASE (ALDH3A1) member of a superfamily of enzymes that uses either NAD+ or NADP+ to inactivate these active aldehydes by oxidizing them to their
THE LENS
LENS
Mostly water and proteins The majority of vertebrate lens proteins are -, -, and - crystallins There are also albuminoids, enzymes and membrane proteins that are synthesized in an epithelial layer
LENS
Other animals have different crystallins. The most important physical requirement of these proteins is that they maintain a clear crystalline state. They are sensitive to changes in oxidation-reduction, osmolarity, excessively increased concentration of metabolites and UV irradiation.
LENS
Structural integrity of the lens is maintained:
for osmotic balance by the Na+/K+ exchanging ATPase
for redox-state balance by glutathione reductase For growth and maintenance by protein synthesis
LENS
The primary role of most lens proteins is to function as crystallins, but many are expressed in other tissues and serve other roles such as enzymes and/or have other functional roles.
LENS
- and - crystallins are SMALL HEAT SHOCK PROTEINS (sHSP) or CHAPERONES help maintain lens proteins in their native, unaggregated states. Their highest expression is in eye lens, but they also occur in other tissues such as skeletal and cardiac muscle where they are involved in filament assembly.
LENS
Mutations in - and - crystallins:
CATARACT FORMATION Possible MUSCLE WEAKNESS and HEART FAILURE
LENS
Energy for these processes comes from the metabolism of glucose. Glucose metabolism in lens tissue (periphery) 85% - glycolysis 3% - TCA cycle Remaining (12%) PPP
LENS
The central area of the lens, the nucleus or core, consists of lens that were present at birth. The lens grows from the periphery and in humans increases in weight and thickness with age and becomes less elastic
LENS
This leads to a loss of near vision, a normal condition referred to as presbyopia. On average, the lens may increase threefold in size and approximately 12-fold in thickness from birth to about age 80
LENS
CATARACT the only known disease of the lens, is an opacity of lenses brought about by many different conditions. Two most common types of cataracts 1. senile cataracts 2. diabetic cataracts
POLYOL PATHWAY
A third cause, especially among young people, is due to inherited mutations in crystallins that function in lens as CHAPERONES. When there are mutations in chaperones that interfere with their function, misfolded proteins can occur and result in cataract formation.
THE RETINA
Mitochondria are present in retinal rods and cones but not in the outer segments where visual
CLINICAL CORRELATION
VISUAL TRANSDUCTION
VISUAL TRANSDUCTION
The tips of the rods and cones penetrate the pigmented epithelial layer of the retina. The pigmented epithelial layer of the retina is: 1. involved in the trans- to cis- retinal recycling phase of the visual cycle, and 2. it also absorbs excess light and prevents reflections back into rods and cones where it may cause distortion or blurring of images. The CHOROID lies behind the retina and contains blood vesicles that supply nutrients to the retina.
VISUAL TRANSDUCTION
The eye may be compared to a video camera, which collects images, converts them into electrical pulses, records them on magnetic tape, and allows their visualization by decoding the taped information. The eye focuses on an image by projecting that image onto the retina.
VISUAL TRANSDUCTION
A series of events begins, the first of which is PHOTOCHEMICAL, followed by biochemical reactions that amplify the signal, and finally electrical impulses are sent to the brain where the image is reconstructed in the minds eye PHOTOCHEMICAL BIOCHEMICAL ELECTRICAL
VISUAL TRANSDUCTION
In effecting this process, the initial event is transformed from a physical event to a chemical event through a series of biochemical reactions, to an electrical event, to a conscious acknowledgement of the presence of an object in the environment outside the body.
VISUAL TRANSDUCTION
Photons (light) are absorbed by photoreceptors in the outer segments of rods or cones, where they cause isomerization of the visual pigment, retinal, from the 11-cis-form to the alltrans-form. The isomerization causes a conformational change in the protein moiety of the complex and affects the resting membrane potential of the cell, resulting in an electrical signal being transmitted by way of the optic nerve to the brain.
CLINICAL CORRELATION
RETINITIS PIGMENTOSA
1. why is it not advisable for teenagers with near sightedness to get Lasix surgery?
LASIK is safe for teens, but it is not recommended for most teenagers. It is best to have LASIK only when you have stopped growing and your eyes have stopped changing, which is frequently in the very late teenage years or during your twenties. If you have LASIK before your eyes stop changing, you will need to come back and have further LASIK after your eyes stop changing
Orlistat (Xenical) works in the gastrointestinal tract, blocking an enzyme that is needed to digest fat. Instead of being absorbed into the body, up to one third of the fat that a person consumes will accumulate in the intestines and be excreted in the stool. Orlistat (Xenical) also blocks the absorption of needed fat-soluble vitamins A, D, E, and K, as well as beta-carotene, so daily vitamin supplements must be taken.
Vitamin A (or Vitamin A Retinol, retinal, and four carotenoids including beta carotene) is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light (scotopic vision) and color vision. Vitamin A also functions in a very different role as an irreversibly oxidized form of retinol known as retinoic acid, which is an important hormone-like growth factor for epithelial and other cells
References
Devlin Biochemistry pp.953-959 Dr. Taylors Lecure
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