NEURO_Biochemistry of Vision

Drugs related to vitamin A

Accutane - retinoic acid Can cause craniofacial, CNS, CV, and thymic malformations

Describe Amacrine Cells

Amacrine cells has a large cell body, a lobulated nucleus, a single process with extensive branches and extends into the inner plexiform layer. Neurotransmitters = gamma-aminobutyric acid (GABA) or glycine

Describe the on and off pathways in the retina

Glutamate is thought to be an inhibitory neurotransmitter that results in the hyperpolarization of the postsynaptic cell which causes a diminution of that cell's neurotransmitter release, it has been now shown that some bipolar cells react in the opposite way because they have a different glutamate receptor protein on their membrane and are actually depolarized (excited) by their interaction with glutamate. It has been determined that there exists an ON pathway and an OFF pathway in the retina. Keep in mind that all photoreceptor cells continue to release the neurotransmitter, glutamate, when totally in the dark. The ON pathway involves bipolar cells that are turned "on" when the photoreceptor cells are exposed to light. Therefore in the dark, while the rods and cones are releasing maximal amounts of glutamate, these bipolar and ganglion cells are inhibited. This in effect keeps the ON pathway turned off. But when the light comes on and interacts with the photo pigment in the photoreceptor cell, this reduces the release of glutamate from the rods and cones. The suppressive effect on the bipolar and ganglion cells is removed and they are able to send their messages along. Therefore, when the light turns on, the ON pathway turns on as well. This system allows us to be able to see light objects on dark backgrounds. The OFF pathway works in the opposite way. When the photoreceptor cells are in the dark and are releasing maximal amounts of glutamate, this depolarizes (excites) the OFF bipolar cells and ganglion cells. This in effect allows the OFF pathway to stay on when the rods and cones are in the dark. But when light strikes the photoreceptors servicing the OFF pathway, the reduction in glutamate release reduces the output from the OFF bipolar and ganglion cells resulting in them turning off. So when the light is on, this system turns off. It is the OFF pathway that allows us to see dark objects against light backgrounds. It's most likely the OFF pathway that you are using right now as you read this column.

Describe glycine

Glycine is another neurotransmitter Glycine is a major inhibitory neurotransmitter Glycine is synthesized from serine

Where do we get glutamate and glycine from?

Glycolytic pathway

Describe Horizontal Cells

Horizontal cells transfer information in a horizontal direction parallel to the retinal surface. They have 1 long axon and several short dendrites with branching terminals. Horizontal cell synapse with photoreceptors, bipolar cells, and other horizontal cells. Horizontal cells are thought to modify cone response but not rods.

Describe the interplay of the cells versus their action potentials

In general, the photoreceptors, the horizontal cells, the bipolar cells and most of the amacrine cells do not have action potentials that result in an "all or nothing" response. They have the ability to release their neurotransmitters at certain voltage levels which can be modulated by the impact of the incoming neurotransmitters released by each other. In other words, the release of glutamate will often cause hyperpolarization of a postsynaptic cell and diminish its release of neurotransmitter. There are many different types of neurotransmitters that are released by different types of interneurons which can either inhibit (hyperpolarize) or excite (depolarize) the postsynaptic cell. The horizontal cells are able to communicate with each other and also sends messages back to the photoreceptors and on to the bipolar cells. Similarly, the amacrine cells seem to be able to contact and affect the actions of other amacrine cells and both bipolar and ganglion cells. These interactions involve many different types of neurotransmitters and the nature of these modifications and their significance for the processing of the visual message before it is sent to the brain is at present under study.

What is light?

Its a photon

Give a schema of how light passes through the retina

Light passes through most of the retinal layers before reaching and stimulating the photoreceptor outer segment discs. The neural flow then proceeds back through the retinal elements in the opposite direction of the incident light. The efficient and accurate performance of the retina is not hampered by this seemingly reversed situation.

Step 1 to how we see

The change in rhodopsin starts a chemical reaction within the photoreceptor cell involving three biomolecules; namely, transducin: which activates the enzyme phosphodiesterase (PDE): which breaks down cGMP (3'5' guanosine mono-phosphate). The drop in cellular cGMP results in the closing of the Na+ and Ca++ ion channels along the cell membrane which hyperpolarizes the photoreceptor's membrane potential. You may recall that when a neuron's membrane potential becomes more negative, this causes inhibition, and for the photoreceptor cell this means the slowing down or complete stoppage of the release of its neurotransmitter, glutamate.

How do bipolar cells communicate with each other?

They use biocemical messengers called neurotransmitters.

Why did pirates wear eye patches?

To help with night blindness 11 - cis - retinal

Discs contain many...

rhodopsin molecules

Describe the different parts between the rod/ cone spherules and their synpases

1. Bipolar cell is a second-order neuron in the visual pathway 2. Rod bipolar cell- 3. Flat midget bipolar cell 4.Invaginating midget bipolar cell 5. Diffuse cone bipolar cells 6. Blue cone bipolar cell 7. Giant cone bipolar cell 8. Horizontal Cell

Describe how a neurotranmitter works.

1. NT synthesis and packaging in vesicles 2. NT release 3. NT reuptake/recycling 4. NT release Receptor Binding (typically covalent binding) 5. Receptor activation of 2nd messenger system

What are the six parts of photoreceptor cells?

1. The outer segment: contains visual pigment molecules for the conversion of light into a neural signal 2. A connecting stalk: the cilium 3. The inner segment: contains the metabolic apparatus 4. The outer fiber: extends from the inner segment to the cell body 5. The cell body: the part which contains the nucleus 6. The inner fiber: ends in a synaptic terminal

Describe photoreceptors

As with rods, the neurotransmitter released by cones is glutamate. When a photoreceptor is depolarized (dark) it releases Glutamate. Glutamate binds to ionotropic receptor on bipolar dendrite, cation channels are opened in the cell membrane causing bipolar cells to depolarize and release Glutamate

Describe bipolar cells

Bipolar Cell: are a second-order neuron in the visual pathway. Bipolar cells relay information from photoreceptors to horizontal, amacrine and ganglion cells and receive extensive synaptic feedback from amacrine cells. Neurotransmitter of choice: Glutamate

Describe retinal detachment. What objects attach the REP layer to the photoreceptor layer?

Clinical case: retinal detachment occurs between the RPE cells and photoreceptors due to the fact that no intracellular junctions join these cells Attachment of REP layer to photoreceptor layer Intraocular pressure Osmotic pressure Fluid transport across RPE Presence of vitreous Microvilli

Describe the ganglion cell layer

Ganglion cell layer is generally a single cell thick except near the macula where it might be 8 to 10 cells thick and the temporal side of the optic disc where it is 2 cells thick

Describe Ganglion Cells

Ganglion cells can be either bipolar (single axon and single dendrite) or multipolar (single axon with more than one dendrite) Neurotransmitter = Glutamate

Give general information about photoreceptors

General Information: The photoreceptor is in the depolarized state when it is not stimulated by light. As neurons usually do in the depolarized state, the photoreceptor secretes its neurotransmitter. During depolarization, voltage-gated Ca++ channels are open and calcium ions facilitate the process by which the vesicles containing glutamate merge with the cell membrane, enabling the release of neurotransmitter into the synaptic

Step 3 to how we see

It appears that the rods and cones do not actually produce action potential spikes like other nerve tissue. In the dark, they are continuously releasing glutamate which in this setting is inhibitory. This means that in general, the rods and cones usually are sending inhibiting messages to their interconnecting neurons. So when a photon of light strikes the photoreceptor and closes its Na+ and Ca++ ion channels resulting in hyperpolarization of the cell membrane, this causes the cell to decrease its output of an inhibitory neurotransmitter (glutamate). Essentially this is like a double negative that results in a positive response. The interconnecting cell which has been previously inhibited by the secretion of glutamate by the presynaptic photoreceptor cell has been released from that inhibition and is free to start sending its own message down the line.

Describe the nerve fiber layer

Nerve fiber layer consists of ganglion cell axons

Step 2 to how we see

Note that this hyperpolarizing response to light that results in the decrease of neurotransmitter release occurs only in vertebrate eyes. Most invertebrate photoreceptor cells depolarize, or are excited, when exposed to light, which will result in an increase of neurotransmitter being released, much like the motor neuron. If you're scratching your head wondering how this hyperpolarizing action would allow us to see, get ready to wonder as you've never wondered before.

Describe the photoreceptor layer

Photoreceptor layer contains the outer and inner segments of rods and cones, projections from the apical surface of Muller cells extend into the PR layer

Describe the RPE layer

RPE consists of a single layer of pigmented cells. There are 4 to 6 million RPE cells and each cell interacts with 30 to 40 photoreceptors

What are signs of vitamin A toxicity?

Teratogenic effects Liver disease Dryness Erythema Scaling/peeling of skin Hair loss Nail problems Headache Nausea Vomiting Bone overgrowth of periosteal bone (Hathcock et al, 1990) Increase in bone fractures

Discuss the biochemistry of the retina pigmented epithelium. What are the 8 pieces?

The RPE is responsible for energy metabolism. The zona occludens which joins the RPE cells is part of the blood-retinal barrier and is responsible for controlling nutrients and metabolism from the choriocapillaris into the retina and removal of waste products.

Visual Cycle

Vision begins with the absorption of light by rhodopsin, causing its 11-cis-retinal to photoisomerize into its all-trans form. All-trans-retinal is liberated from rhodopsin (an integral membrane protein representing approximately 75% of the total membrane proteins in retinal photoreceptor membranes) in photoreceptor cells and is rapidly and enzymatically reduced to all-trans-retinol (vitamin A). For vision to continue, 11-cis-retinal must be regenerated in the eye, as this is the only organ in the body where 11-cis-retinoids are found. The actual biological site of isomerization is in the retinal pigment epithelium (RPE), the organ found behind the retina in vertebrates. When vitamin A is produced in the photoreceptors, it is transported into the RPE where it is esterified by lecithin retinol acyl transferase (LRAT) and isomerized with hydrolysis to 11-cis-retinol. Oxidation by 11-cis-retinol dehydrogenase in the RPE to 11-cis-retinal completes the visual cycle.

Discuss vitamin A

Vitamin A exist in three main forms Retinol (Alcohol form) Retinal (Aldehyde form) Retinoic Acid (Acid form) Plants and carotenoids -carotene Significant Sources of Vitamin A Liver, dark green leafy vegetables, yellow-orange vegetables, fruit & fortified foods

What is Vitamin A?

another term for retinol

Rhodopsin molecules contain...

retinal and opsin