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Josh-D. S. Davis

Xaminmo / Omnimax / Max Omni / Mad Scientist / Midnight Shadow / Radiation Master

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The aspiration to truth is more precious than its assured possession.
Josh 201604 KWP
So I was researching eye color, and it took me off on a journey. Here's what I've found on topic one, so far.

In a study, rats were exposed to 5kJ/m2 of 300nm UV Radiation for 15 minutes. 1 week later, the lenses were examined for the results. Pigmented eyes with constricted pupils protected the lenses from UV-induced cateracts. Dilated pupils in pigmented and albino eyes suffered moderate cateracts. Constricted pupils in albino eyes suffered the worst cateracts.
Source: Photobiology

The current evolutionary picture pieced together by fossil, anthropological, & DNA evidence looks like this: Around 200,000 years ago ancestors to modern humans radiated out of Africa during periods of inter-glaciation [between Ice Ages]. Equatorial Africa on the savanna gets a lot of direct UV.

Melanin protects humans from excessive UV and the resulting cancers/cellular damage. As hominids migrated to extreme latitudes North, the UV diminished.

UV is necessary for synthesis of vitamin D. Natural selection worked to confer a survival advantage to those humans with low melanin. The children of low-melanin northern humans had a better supply of vitamin D.

Those children had a better chance of producing more, healthier children. Northern people got light-skinned, blonde, & blue-eyed from lack of melanin. Their descendants migrated south as the glaciers rose again, spreading the genes.
Source Franklin Institute

- Two brown-eyed parents can easily have a blue eyed child.
- Two completely blue-eyed parents CANNOT have a fully brown-eyed child with normal eye development except in certain extremely rare circumstances.
- The gene for brown/blue eyes is EYCL3 found on Chromosome 15.
- The gene for green/blue eyes is EYCL1 found on Chromosome 19.
- Brown is the result of melanin deposits in the iris.
- Green is the result of [this is debated] lipochrome deposits in the iris.
- Blue-grey [and in some albinism, pink] is due to a lack of pigment in the iris.

The underlayer, called the stroma, reflects light through its cells like a mirror's silver back. How the pigment is distributed over the iris involves other genes which produce flecks, rays, rings, partial diffusion or full diffusion. This inheritance is very complicated and the genes have not been well identified.

Here are some reliable sources:
Source Franklin Institute referencing NIH.

Factors in eye color
Stroma (muscle/ligament) depth
Stroma collagen thickness and arrangement
Iridic Ring (artery rim around the pupil in the muscle)

Anterior Border Layer, or Iris Pigment Epithelium
There are conflicting definitions here, but since "epi" means
"above", I'll assume the one stating that the IPE is behind
the iris is WRONG.

I've seen info saying the only eye pigment is melanin.
I've seen it described as brown to yellow or only brown
I've seen info stating melanin is the brown, and
lipochrome/lipofuscin is the yellow

Some say the depth of individual stroma cells darken the eyes and refract.
Some say it's the thickness of the stroma collagen.

Eye colors
Pink / Red = no pigment, no stroma reflection. Color is from capilaries.
Violet = Pink/red with stroma blue reflection
Blue = little pigment, stroma reflects blue
Grey = little pigment, stroma reflects blue
Green = light pigment (or lipochrome), stroma reflects blue
Hazle = transition between green and brown
Brown = much melanin blocks more light.
Black = this is dark brown

darker ring near pupil is from iridic artery
spots are late genetic mutations, freckles, or othe clumps of melanin producing cells
different colored eyes are early genetic mutations or neurological
streaks are variances in stroma depths
Source: Many sites on the web

Melanocytes require innervation to survive

Heterochromia Different colored eyes
nerological, hereditary, developmental or tumor
Heterochromia iridis - different areas of the iris colored differently
clump cells (dark spots), birth marks, tumors, and growth pattern
source: BBC article

The melanocyte is the melanin-producing cell of the epidermis. Melanocytes (MCs) are derived from neural crest cells [91], which emigrate out of the dorsal area along the entire length of the neural tube. These melanoblasts (MBs) migrate throughout the mesenchyme of the developing embryo and home into specific target sites, predominantly in the basal cell layer of the epidermis and hair bulbs of the skin, the uveal tract of the eye, the stria vascularis of the inner ear and the leptomeninges of the brain. The concept of a ‘melanocyte organ’ has been proposed.

At these sites, the MB differentiates into the melanin-producing cell (MC) synthesizing a melanosomal granule within which the substrate tyrosine is subsequently converted to melanin polymers. Pigmented melanosomes can then be transferred to keratinocytes (KCs) in the skin or retained by MCs in extra-cutaneous sites.

There are two major types of melanin: the eumelanins (brown and black pigments) and the pheomelanins (red and yellow pigments).

In humans, melanins have a major role in the skin where they are responsible for color and photoprotection against sunlight. Melanins in the eyes play a role in light absorption and in free radical scavenging [39]. MCs in the inner ear are required for the development and normal function of the cochlea. Melanin per se may protect against traumata to the cochlea [104].

Certain regions in the brain are pigmented by neuromelanins. In the substantia nigra, loss of pigment is associated with Parkinson’s disease [89]. MCs in the different organs exhibit unique functions. MCs in the resident organs show functions of protection and regulation similar to those of nerve cells.

MelanoCytes are cholinergenic neural cells. Interruption of acetylcholine pathways will restrict melanin production as will an increased tone of adrenergenic pathways.

UVB exposure causes MelanoBlasts to produce melanocytes, which migrate outwards. In the skin, this is from resistant/protected hair outer root sheath (ORS).
Somewhere in there, I saw that tyrosine recption is signifigant to melanocyte migration pathways.
Source "Melanocyte Destruction and Repigmentation in Vitiligo: A Model for Nerve Cell Damage and Regrowth", Hsin-Su Yu, Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

There are six kinds of chromatophores, each recognized by its color. The light absorbing chromatophores are the melanophores (brown), erythrophores (red), cyanophores (blue), and xanthophores (yellow). Melanophores are full of melanin-filled granules, melanosomes, which gives the cells their characteristic dark brown color. Leucophores (white) and iridophores (metallic) lack color and their particles reflect light.

All classes of chromatophores can regulate the integument color, although this thesis is focused on melanophores. The dark melanophores can either hide colorful cells so that the animal appears dark, or expose colors from underneath, see Figure 1. Variations in the environment are detected and the animal regulates its colors and patterns via communicating nerve cells and hormones in the blood stream, which affect the melanophores. In response to hormonal or neural stimulation, pigment granules migrate toward or away from the cell center in an ordered manner. Hormones as well as neurotransmitters act on transmembrane receptors located on the melanophore cell surface.

Aggregation of melanosomes to the cell center in [pictures in this article] is a result of melatonin stimulation.

Melanosomes in fish and amphibians disperse throughout the cytoplasm when α-melanocyte stimulating hormone (α-MSH), a tridecapeptide secreted from the intermediate lobe of the pituitary.

α-MSH is secreted when fishes are on a dark background and the scales accordingly appear dark. The α-MSH secretion is inhibited when fishes have a light surrounding and thereby the scales lighten (Ganong 1993).

Melanin concentrating hormone (MCH) is a heptadecapeptide that can bring about a lightening in the scales of neopterygian fish. MCH thereby antagonizes the darkening caused by α-MSH. The MCH peptide is secreted from the neurohypophysis and it acts by concentrating pigment granules to the center of melanophores.

Noradrenaline from the sympathetic division of the autonomic nervous system and adrenaline from the adrenal medulla regulate the distribution of melanosomes differently, depending on the type of adrenergic receptor activated in melanophores.

Activated α-adrenoceptors mediate aggregation of melanosomes, and activated β-adrenoceptors mediate dispersion. Melatonin-stimulation of melanophores results in aggregation of melanosomes in amphibians, although its effect is not always apparent in fish. Melatonin synthesis in the pineal gland follows a 24-hour rhythm, reaching maximum in the dark period of the day. Visible light leads to dispersion of melanosomes in Xenopus laevis melanophores (Daniolos, Lerner et al. 1990) and the signal is conveyed by a seven transmembrane photoreceptor, melanopsin (Provencio 1998).

Pigment movement in melanophores is regulated by the intracellular concentration of adenosine 3’,5’-cyclic monophosphate (cAMP). High levels of cAMP lead to dispersion and low levels cause aggregation of melanosomes.
I wonder if any of these pathways still exist in humans? How much darker are we in the sunlight versus at night when sleping and melatonin levels have risen versus seratonin?
Melanosome dispersion requires the activity of serine threonine protein kinases and aggregation requires serine threonine protein phosphatase activity.

The transport system responsible for the ordered movement of melanosomes consists of cytoskeletal tracks and motor proteins that move melanosomes along these tracks.

The cytoskeleton is commonly divided into microtubules, actin filaments and intermediate filaments, of which microtubules and actin filaments have been shown important in melanosome movement.

Motor proteins are multimeric enzymes that convert energy from adenosine triphosphate (ATP) hydrolysis into directed movement along the cytoskeleton.
Melanosomes initially move to the periphery along radial microtubules and then continue their movement along randomly oriented actin filaments. Actin filaments are utilized for achievement of uniform distribution of melanosomes in the dispersed state.

Cytoplasmic dynein governs aggregation (clumps melanosomes together). Kinesin II is responsible for fast dispersing movement (traversion along microtubules). Myosin V is required for short-range spreading of melanosomes in fish. In frog cells, myosin V tethers melanosomes to actin filaments. This continues long-range dispersion, prevents aggregation by cytoplasmic dynein, and helps maintain dispersion. Disruption of actin fibers leads to hyperdispersion due to kinesin II activity.

Cytoplasmic dynein and kinesin have important roles in microtubule-based melanosome transport in human melanocytes.
Source: http://www.ep.liu.se/diss/med/06/59/digest.pdf
"Signaling for color change in melanphores and a bioseneor application", 2001, Annika Karlsson, Linköping Universitet, Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, SE-581 85 Linköping, Sweden

Cryptochromes, which come in two forms called CRY 1 and CRY 2, are linked to vitamin B-2 and located in a different part of the retina.

Cryptochromes enable animals and humans to synchronize their circadian clocks by absorbing blue light and transferring the light signal through the optic nerve to a different part of the brain from the center for vision.
Source: http://www.eurekalert.org/pub_releases/1998-11/UoNC-DECN-191198.php

Wakefulness cycles are normally driven by Oscillating activity in the SupraChiasmatic Nucleus of the HypoThalmus which:

1. Receives direct afferents from the Retina
2. Projects to the PreOptic Nucleus of the HypoThalamus
3. Has a light-dark circadian rhythm that can be detected in Sympathetic Axons that innervate the Pineal Gland from the Superior Cervical Ganglion.

As a result, there is light-entrained rhythmicity to secretion of Melatonin and its precursor, Serotonin, from the Pineal (more is secreted in darkness). Little is known about which organs take cues from this Pineal Clock.
Source: http://www.albany.net/~tjc

Schwann Cells - are cells of the Peripheral Nervous System (PNS) that make and maintain its Myelin as well as the formation of the Neurilemma.

Oligodendrocyte Cells - are Myelin forming cells of the CNS that produce, maintain, and repair Myelin Sheaths surrounding Axons. Each section of CNS Myelin (InterNode) is the CytoPlasmic Process of a single OligoDendroCyte that simultaneously maintains numerous InterNodes on many different Axons. The loss or injury to one of these cells, produces multiple DeMyelinated areas on many different Axons.

During development, the PolySialylated form of the Neural Cell Adhesion Molecule NCAM, PSA-NCAM, is expressed at the Axonal surface, and acts as a negative regulator of Myelination, presumably by preventing Myelin-forming cells from attaching to the Axon.

Nodes of Ranvier - Are the only gaps between Myelin sections (InterNodes) along Myelinated Axons, where Sodium (Na+) and Potassium (K+) can be exchanged (Salatory Conduction); hence, continuing the Nerve signal's rapid transmission, to its target. They are crucial electrical refresher sites, where Action Potentials are restored.

Gliosis (Glial) - Scars that are produced by enlargement of Astrocyte processes. When a portion of the CNS is damaged (Neuron or Axon), Astrocyte processes enlarge and replace the damaged tissue. This process is referred to as Gliosis, while the resulting permanent scar tissue is called Plaque (Sclerosis).
Source: http://www.albany.net/~tjc

I found is that UV causes regeneration or melanocytes from melanoblasts, both of which come from the neural tube. Tyrosine is a trigger for melanocytel migration. I'm looking to see if tyrosine is used for other neurons.

The oligocyte is the cell body, and the myelin sheaths are like it's feet. It extends feet to encase an axon based on it's electrical potential. It's attracted to the axons. If there are antibodies or plaques covering the axons, then the oligodendrocytes aren't attracted

What seems to happen is that antibodies kill odd the oligodentrocytes, and when one dies, then all of it's myelin feet die, which leaves SEVERAL axons with gaps. If there are adhesion molecules on the axons, then surrounding cells don't take over, so astrocyte cells take over and form plaques over the gaps. This way, the cells get to keep being fed, and the sodium channel continues to function, but it's not an accelerator like the Oligodendrocytes.

What happens is that the skin of the axon is no longer properly charged. while there may be some shorting, there is also resistance, capacitance, loss of conductance, and crosstalk. The shorting isn't as signifigant due to the low voltage and the fact that there are other glial cells which hold the overall structure together.

Steroids are used to suppress immune reaction and reduce swelling for short duration exacerbations.

Steroids -- Prednisone, Prednisolone, MethylPrednisolone, Betamethasone and Dexamethasone -- are all produced naturally by the adrenal glands in response to stimulation by AdrenoCorticoTropic Hormone (ACTH) from the Pituitary Gland.

The Anterior Pituitary is Glandular. A stalk links the Pituitary to the HypoThalamus, which controls release of Pituitary Hormones. The Posterior Pituitary is used to store Hormones until they are needed.

The HypoThalamus plays an important role in controlling the Endocrine System because it regulates the Pituitary Gland's secretion of several Hormones: Cortisol, AntiDiuretic Hormone (ADH), Oxytocin, Growth Hormone (GH), Thyroid Stimulating Hormone (TSH), AdrenoCorticoTropic Hormone (ACTH), Lipotropins, ß Endorphins, Melanocyte Stimulating Hormone, Luteinizing Hormone, Follicle Stimulaing Hormone, Prolactin

The HypoThalamus regulates the secretory activity of the Pituitary Gland, and in turn, its activity is influenced by Hormones, by Sensory input from the CNS, and by the Emotional state of the individual.

Hormones influence functions as diverse as: Metabolism, Reproduction, Responses to Stressful Stimuli and Urine Production. Afferent fibers that terminate in the HypoThalamus provide input from the following:
* Visceral Organs
* Taste Receptors of the Tongue
* The Limbic System (involved in Responses to Smell);
* Specific Cutaneous areas such as the Nipples and External Genitalia
* The PreFrontal Cortex of the Cerebrum carrying information relative to Mood through the Thalamus

Efferent fibers from the HypoThalamus extend into the BrainStem and the Spinal Cord where they Synapse with Neurons of the Autonomic Nervous System (ANS).

Other Fibers extend through the Infundibulum to the Posterior portion of the Pituitary Gland; some extend to Trigeminal and Facial Nerve Nuclei, to help control the head muscles that are involved in Swallowing; and some extend to Motor Neurons of the Spinal Cord to stimulate Shivering.

The HypoThalamus is very important in a number of functions, all of which have Emotional and Mood Relationships. Sensations such as Sexual Pleasure, Feeling Relaxed, Good, Rage and Fear are related to HypoThalamic Functions.

B-Cell Lymphocytes - are responsible for Humoral Immune Responses, they produce ImmunoGlobulins (AntiBodies) to fight ExtraCellular infections (Bacteria, Fungus, etc.).
Suppressor T-Cell Lymphocytes - supress B-Cell activity and seem to be in short supply during a MS attack (exacerbation).
Source: http://www.albany.net/~tjc