**4. Functional aspects of melanocytes**

Although melanocytes are distinguished for their ability of skin pigmentation, but this is possibly not the single occupation of these pigment bearing cells. In fact, melanocytes have plentiful enzymes which are proficient in biochemical, genetical, and functional association to the immune system as well as antimicrobial protection [72].

### **4.1. Cutaneous pigmentation**

Cutaneous pigmentation is the product of two crucial events: biosynthesis of melanin granules within melanocytes and their subsequent transfer to the neighboring keratinocytes. Though the quantity of melanocytes in all human races is basically invariable, the amount, size, and the way in which melanosomes are spread within keratinocytes may differ [1]. The quantity of melanin granules of human epidermal melanocytes is diverse not only among different skin types but also among different locations of the skin from the same person [73]. This diversity is vastly controlled by gene expression of melanosomal proteins, which regulate the complete activity and expression of melanosomal proteins inside the particular melanocytes [74]. It has been noticed that those melanocytes having low quantity of melanin pigment, produce TYR very slowly but degrade it very rapidly, than melanocytes having higher quantity of melanin pigment and TYR activity [75]. Indeed, darkly pigmented skin possesses several single, large (0.5–0.8 mm in diameter), elliptical, highly electron dense melanosome particles of Stage IV. However, the lighter skin pigmentation is linked with smaller (0.3–0.5 mm in diameter), immature, less dense melanosomes of stages II and III which remain clustered in membranebound groups (FIGURE 4) [76]. These varied configurations of melanosome stages or types as well as distribution exist since birth and are not influenced by external factors (such as sun exposure). They are liable for wide range of skin tones [26].


**Figure 4.** Variations in human skin pigmentation due to different types of melanosomes within epidermal melano‐ cytes.

#### **4.2. Protection from Ultraviolet Radiations (UVR)**

The principal function of melanin is to protect the skin from harmful effects of sunlight, a task accomplished by its capability to scatter and absorb ultraviolet light [77]. So the primary role of melanocytes is to act as natural sun block. Adaptive pigmentation or tanning is the natural physiologic response of the skin against exposure of UVR. Melanin bearing melanocytes, situated in the basal layer of epidermis have vital tasks in the skin's barrier function by preventing damage by UVR. In the basal layer of the epidermis, melanin pigment creates a protective cover over the nuclei of keratinocytes; in the outer layers, they are more evenly distributed. Melanin absorbs UV radiation, thus protecting the cell's nuclei from DNA (deoxyribonucleic acid) damage [78]. UV radiation induces keratinocyte proliferation, leading to thickening of the epidermis [79]. Hence, it is concluded that the tanning involves both an increase in the amount of melanin pigment and epidermal thickening. Both changes serve to increase melanin accumulation in the epidermis, so that the skin is better protected against subsequent UV exposures [80].

#### **4.3. Determination of eye color**

**4.1. Cutaneous pigmentation**

272 Muscle Cell and Tissue

cytes.

exposure). They are liable for wide range of skin tones [26].

**4.2. Protection from Ultraviolet Radiations (UVR)**

Cutaneous pigmentation is the product of two crucial events: biosynthesis of melanin granules within melanocytes and their subsequent transfer to the neighboring keratinocytes. Though the quantity of melanocytes in all human races is basically invariable, the amount, size, and the way in which melanosomes are spread within keratinocytes may differ [1]. The quantity of melanin granules of human epidermal melanocytes is diverse not only among different skin types but also among different locations of the skin from the same person [73]. This diversity is vastly controlled by gene expression of melanosomal proteins, which regulate the complete activity and expression of melanosomal proteins inside the particular melanocytes [74]. It has been noticed that those melanocytes having low quantity of melanin pigment, produce TYR very slowly but degrade it very rapidly, than melanocytes having higher quantity of melanin pigment and TYR activity [75]. Indeed, darkly pigmented skin possesses several single, large (0.5–0.8 mm in diameter), elliptical, highly electron dense melanosome particles of Stage IV. However, the lighter skin pigmentation is linked with smaller (0.3–0.5 mm in diameter), immature, less dense melanosomes of stages II and III which remain clustered in membranebound groups (FIGURE 4) [76]. These varied configurations of melanosome stages or types as well as distribution exist since birth and are not influenced by external factors (such as sun

**Figure 4.** Variations in human skin pigmentation due to different types of melanosomes within epidermal melano‐

The principal function of melanin is to protect the skin from harmful effects of sunlight, a task accomplished by its capability to scatter and absorb ultraviolet light [77]. So the primary role of melanocytes is to act as natural sun block. Adaptive pigmentation or tanning is the natural

The external origin of eye color is determined by the distribution and quantity of melanocytes in the uveal tract of the eye. The amount of melanocytes does not vary between eye colors [81], but it is the intracellular melanin content, types, and its packaging within the melanosomes that vary, which provides a wide variety of eye colors. There are two forms of melanin pigment particles (skin and hair melanocytes) produced during melanogenesis and both occur in the iris of the humans [82,83]. The quantity and types of melanin in the iridal melanocytes vary with iris color. However, unlike the skin and hair in which melanin is produced continuously and secreted, in the eye the melanosomes containing the pigment are retained and accumulate in the cytoplasm of the melanocytes within the iris stroma. White light entering the iris can absorb or reflect a spectrum of wavelengths giving rise to the three common iris colors: blue, green-hazel, and brown. Even though blue colored eyes have same number of melanocytes but they posses low melanin pigment and few melanosomes; green-hazel color of irides are the outcome of average number of melanin granules as well as melanosome number; and brown colored iridies are the product of huge numbers of melanin granules along with melanosome particles [84].

#### **4.4. Other incomparable abilities of melanocytes**

Melanocytes are now beginning to take more and more fascinating roles in other tissues of the body. The existence of melanin and melanocytes are not limited to the skin, hairs, and RPE [85] only, besides, they are reported to be present in the leptomeninges, stria vascularis of the cochlea, in the heart, as well as in the substantia nigra and locus coeruleus of the brain. They have also been verified to function in hostile regions of our body, such as adipose tissues. In stria vascularis of the cochlear melanocytes remains present as intermediate cells. The stria intermediate cells play crucial role in the initiation of endolymph-mediated action potentials that is essential for normal hearing. Melanin granules produced by melanocytes in the inner ear even play important roles in body balance [86].

Extracutaneous melanocytes located in the brain may have several neuroendocrine functions. Pigment granules found in brain are known as neuromelanin, consists of giant, dense eume‐ lanin covered pheomelanin core which may also include aliphatic and peptides [87]. Neuro‐ melanin is predominantly confined to dopaminergic neurons of substantia nigra as well as in the locus coeruleus, and ultimately gets accumulated in the human substantia nigra with age [88]. Several researches have favored the view that neuromelanins have a defensive role by binding/elimination of reactive oxygen species (ROS) along with metals that would otherwise be extremely toxic to neurons [89]. In a recent study, it has been reported that nearly all brain tissues hold significant quantity of neuromelanin, which is supposed to play crucial tasks in reducing organ toxicity [90].

Interestingly, it has been observed that melanocytes are also situated in the valves and septa of heart [91]. It was further hypothesized that the origin of cardiac melanocytes may take place from the same precursor population as that of skin melanocytes because of its dependency on the same signaling molecules which is needed for the appropriate development of skin melanocytes [92], but their exact function in this location is still unclear. The synthesis of melanin is not always beneficial, either in heart or in other tissues, for example, in the lungs where in an unusual ailment known as Lymph angioleio myomatosis (LAM) [93], the muscle cells slip back into their developmental stages along with the expression of melanocytes like specific markers Pmel17, tyrosinase, etc. The resulting production and accumulation of melanin in lung tissues is eventually lethal.

Randhawa *et al.* [94] reported that the biosynthesis of melanin also occurs in the adipose tissue of morbidly obese humans. It was also assumed that the ectopic synthesis of melanin in the cytosol of obese adipocytes possibly provide a balanced mechanism to work as anti-inflam‐ matory factor as well as it decreases the oxidative damage. In the course of enhanced deposition of cellular fat, adipocytes become more exposed to endogenous apoptotic signals especially with ROS, which could be counteracted by ectopically produced melanin. In addition, adipocytic melanin may also suppress the secretion of proinflammatory molecules [3].
