Lecture 5/1

Definition of Physical Color: Color is described as a physical property of light waves determined by frequency
- High Frequency Light: Violet
- Low Frequency Light: Red
- Intermediate Frequencies: Yellow, green, orange, etc.
Human Perception vs. Physics: While frequencies coexist like singers in harmony and do not physically interact, the human brain perceives overlapping frequencies (e.g., red and green) as a single color (yellow).
The Overlap Phenomenon: When red and green lights overlap, the region appears yellow to the human eye, even if no actual yellow-frequency light is present. This is a biological artifact of how the retina processes signals.

Eye Components: The eye includes the cornea, pupil, lens, iris muscles (used for focusing and light regulation), and blood vessels for oxygen supply.
The Retina: A thin layer of neurons located at the back of the eyeball.
- Retinal Pigmented Epithelium (RPE): The layer situated just behind the retina
  - In non-nocturnal species (like humans), it primarily absorbs light.
  - In nocturnal animals, the RPE is more reflective (causing the "glowing" eye effect), allowing light to bounce back into photoreceptors for a "second chance" at detection in low-light conditions.
- Optic Nerve: A bundle of axons that transmits signals from the retina to the brain.
- Blind Spot: The specific area where the optic nerve exits the retina; it lacks photoreceptors. The brain masks this gap by continuously scanning and filling in data.
- Fovea: The central region of the back of the eye where light is focused most accurately. It contains the highest concentration of cone cells.

Rods:
- Specialized for low-light conditions.
- Only one type of rod cell exists in humans.
- Signals are binary (light vs. no light), providing no capacity for color discrimination.
Cones:
- Specialized for color detection.
- Three distinct types corresponding roughly to wavelengths:
  - 1. L (Long Wavelength): Associated with the color red.
  - 2. M (Medium Wavelength): Associated with the color green.
  - 3. S (Short Wavelength): Associated with the color blue.
The Trichromatic System: Human vision uses these three detectors to simulate the entire spectrum of physical colors. TV manufacturers utilize this property by only using Red, Green, and Blue (RGB) pixels to trick the brain into seeing all colors.

Ectodermal Origins: Eye structures are derived from the neuronal and surface ectoderm of the head.
Developmental Stages:
- 1. Optic Grooves: Initial invaginations in the neural tube.
- 2. Optic Vesicles: Elaborated structures from the grooves.
- 3. Lens Placode: Formed from surface ectoderm through signaling between the ectoderm and the optic vesicle.
- 4. Optic Cup: The precursors to the final eye structure.
Retinal Progenitor Cells (RPCs): These are multipotent cells capable of becoming any photoreceptor type.
Differentiation Pathway:
- Initial decision: RPC becomes either a Rod or a Cone Progenitor.
- Cone Progenitor decision: Becomes either an S Cone or an M/L Progenitor.
- Final decision: The M/L progenitor randomly differentiates into either an M Cone or an L Cone.

Opsins: G-protein coupled receptors activated by light.
Rhodopsin: Found in rods.
Photopsins: The S, M, and L opsins found in cones.
Gene Duplication: The M and L opsin genes are the result of a relatively recent gene duplication event.
- They are located very close together on the X chromosome.
- They share a promoter region called the LCR (Locus Control Region).
- The LCR randomly activates one gene and silences the other permanently for that specific cell.
Evolutionary History: Old World primates (Africa and Asia) share a common ancestor that experienced this duplication, leading to trichromacy (three-color vision).
- Ancestral lineages were dichromats (two-color vision) for a significantly longer period.
- Some modern organisms, like the mantis shrimp, have significantly more opsin types and superior color vision compared to humans.

S-Cone Distribution: Developmentally regulated through signaling; humans generally have a lower percentage of S cones, making blue light appear dimmer than red or green at the same intensity.
L and M Distribution: This is random and highly variable between individuals. * Research indicates a range from $27\%$ to $70\%$ for L-cone distribution in different people.
Sex-Linked Traits: Because M and L opsins are on the X chromosome, color vision deficiencies are more common in males (who have only one X chromosome).
Phenotypes:
- Protanopic: Mutation in the L-opsin gene (lacks red detection).
- Deuteranopic: Mutation in the M-opsin gene (lacks green detection). Both are often grouped as "red-green color blindness."
- Trityanopic: Mutation in the S-opsin gene. This is located on a non-sex chromosome (autosome); therefore, an individual must have two mutated alleles to express the phenotype. It is much rarer.

Structure of Cone and Rod Cells:
- Inner Segment: Contains the nucleus, mitochondria, endoplasmic reticulum (ER), and Golgi apparatus.
- Axon: Projects signals back to other retinal neurons.
- Outer Segment: A highly specialized primary cilia structure consisting of membrane invaginations (discs).
Outer Segment Formation: Does not develop until after birth to save energy, as there is no light stimulus in the womb.
- In mice, elaboration begins around day $6$ ( $p6$ ).
- Requires a massive increase in vesicle transport for membrane and opsin protein delivery.
Connecting Cilium: A narrow region with a $9+0$ microtubule doublet arrangement (nine doublet microtubules, no central pair).
Basal Body: The mother centriole from the centrosome located at the base of the cilia.

Membrane Curvature: High curvature at the edges of the discs is induced by proteins.
- Specifically, a protein called perforin (identified in the transcript as such) is found on the periphery of the discs to induce the necessary bending.
Intraflagellar Transport (IFT):
- Dynein Motors: Move components from the Golgi toward the minus ends (transiently toward the centrosome/basal body).
- Kinesin Motors: Move components (like opsins) toward the plus ends (the distal tip of the outer segment).
Ectosomes vs. Discs:
- Normal cells bud off membrane-bound vesicles called ectosomes (or exosomes) using Escort proteins (rather than Dynamin, which is used for inward budding).
- Photoreceptors use the same pathway but stop before the vesicle pinches off, resulting in the formation of a disc.
- RDS Mutants: Mutations in the RDS protein cause the cells to fail at disc formation. Instead, they produce a mass of free-floating ectosomes filled with opsin proteins.