Retina Biochemistry Flashcards
What are photon detectors?
Opsins + 11-cis-retinal. Cells which turn a photon of light into an electric signal (happens in photoreceptors)
How are eyes related to the brain?
The eye is an extension of the brain. Eyes receives visual input and send neural signal to brain for interpretation. The brain in turn may send signals for eye movements to gain additional information for processing. The brain may send signals received from elsewhere (ex: auditory cues) to direct eye movements.
What are the main classes of retinal cells?
photoreceptors, bipolar cells, ganglion cells, horizontal cells, and amacrine cells
What are the human photoreceptors?
Specialized type of neuron found in the retina that is capable of phototransduction. Rods, Cones, and photosensitive ganglion cells ( do not contribute to sight directly, but are thought to support circadian rhythms and pupillary reflex).
What are the major groups of opsin? And how are they different?
Opsins are membrane proteins (visual pigments that are vitamin A based chromophore) that form a long helix that loops back and form across the membrane bilayer (7 times) and it determines wavelength absorbed by a photoreceptor.
2 Major groups: (G-protein coupled receptors)
R-opsin (Rhadomeric); rhabdomeric photoreceptors depolarize to light (Invertebrate)
C-opsin (Ciliary); ciliary vertebrate rods and cones hyperpolarize to light (Human)
Additional information from power point:
Scotopsins (rod rhodopsin), Photopsins (cone rhodopsin), Metarhodopsin
Where does phototransduction occur?
Retina, more specifically in the photoreceptors. Visual pigments photoreceptors in outer segment absorb light initiating biochemical changes to hyperpolarize cell. Signal passes to bipolar and horizontal cells (some organization and processing occurs) onto amacrine and ganglion cells (more organizing and processing) until ganglion cell is activated and sends message to brain via an axon.
Why is vitamin A important in phototransduction? What are the different forms of vitamin A?
It provides a precursor for 11-cis retinal. Vitamin A cannot be synthesized by humans and must be received through diet. Rods and Cones contain the light-absorbing chromophore 11-cis retinal . The essential precursor for this is an all-trans-retinol (aldehyde Vitamin A). Deficiency in Vitamin A may lead to night blindness and dry ocular surface.
Different forms: Retinol (alcohol)- transport, Retinal (aldehyde form)- visual transduction, Retinoic Acid- synthesis, Retinyl Ester- storage
What can mutation of rhodopsin lead to?
Retinal Degeneration. One example is Retinitis pigmentosa (retina slowly and progressively degenerates; common symptoms include difficulty seeing at night and a loss of peripheral vision). Another example in the slides is LCA. Leber congenital amaurosis is a severe early-onset form of retinal degeneration, in which poor vision associated with nystagmus is evident early in childhood.
Rho = RP; RPE65 = LCA; ABCA4 = Stargardt
What are the properties of rhodopsin? Site for binding of prosthetic group? Phosphorylation sites?
Rhodopsin is a G-protein coupled receptor (7 transmembrane helical loop, 348 amino acids) with C terminal being inside cell and N terminating outside of cell. 11-cis retinal is the antennae (prosthetic group at amino acid Lys 296) and activates when it undergoes a confirmation to a trans state. Phosphorylation of Ser & Thr on the cytoplasmic side of the protein inactivates the protein.
What is the role of 11-cis-retinal? Its isomerization?
The 11-cis retinal in photoreceptors determines wavelength absorbed by a photoreceptor. It isomerizes into all-trans retinal (makes rhodopsin change shape).
What is the activated form of rhodopsin?
Rh* (photoisomerized), which activates heterotrimeric Gt by GTP-GDP exchange.
Metarhodopsin II
What is the phototransducing pathway?
Remember this is for rods. The pathway for cones is still not fully understood. Since it can be confusing, I found a great supplemental youtube video explanation. It’s worth the watch. https://www.youtube.com/watch?v=CqN-XIPhMpo
Once rhodopsin changes shape and is activated (from 11-cis retinal going to all-trans-retinal), the alpha subunit comes off of the G protein transducin and binds to phosphodiesterase (PDE). PDE can now take available cGMP and hydrolyzes it to GMP (reduces cGMP concentrations and increases GMP). Normally cGMP keeps local sodium channels open. With decreasing cGMP, the sodium channels close (less sodium and calcium entering cell) allowing hyperpolarization which turns the rods off (normally they are on, depolarized). The rods turning off will release less glutamate, acting on glutamate receptor on the bipolar cell which interacts with amacrine cells that interacts with retinal ganglion cell, sending a signal to brain.
How does transducin work?
3 subunit transducin is attached to rhodopsin. Once rhodopsin undergoes confirmation, alpha subunit will come off (Gtα-GTP). It will bind to PDE thereby activating it to hydrolyze cGMP.
How does PDE work?
Once activated by Gtα* binding, PDEαβ will hydrolyze cGMP to GMP.
What is dark current? What neurotransmitter is involved?
Dark current is the flow of sodium in (outer segment) and out (lower segment?) of the rod when not being stimulated by light. Dr. Koh’s notes say: “Maintain a steady inward current in darkness and depolarize the cell sufficiently (~−30 mV) to sustain synaptic transmitter (glutamate) release.”
