This document discusses melanogenesis and photobiology. It begins by introducing melanocytes and melanin synthesis within melanosomes. It describes melanosome maturation and transfer to keratinocytes. The document then discusses sources of UV radiation and its interaction with skin, including DNA photodamage and repair mechanisms. Finally, it covers the acute and chronic clinical effects of UV radiation exposure, such as erythema, tanning, skin cancer and photoaging.
3. INTRODUCTION
• Melanocytes are specialized cells of the
epidermis and hair follicle whose primary
function is to synthesize and transfer melanin
to adjacent keratinocytes.
• Melanin synthesis occurs in specialized
organelle called the melanosome.
4. • In individuals with different racial
backgrounds, the melanocyte number is
similar.
• But the number, size and distribution of
melanosomes gives the difference in
pigmentation.
9. PERIOD OF
GESTATION
ACTIVITY
Day 10.5 - 11 Master melanocyte transcription factor(MITF) is
expressed in melanoblasts
11.5 Melanoblasts move to MSA
12.5 Melanogenic enzymes DCT , TYRP 1 are expressed
12.5 – 13.5 Melanoblasts migrate through dermis and enter
epidermis in a synchronous wave
14.5 Melanocytes express enzyme Tyrosinase
15.5 Epidermal melanoblasts migrate and populate hair
follicles
16.5 Display pigmentation
10. Melanin
Eumelanin
• Brown/black
• Composed of
– DHI (5,6 dihydroxy indole)
1. Insoluble in strong alkali
2. Black colour
– DHICA (5,6dihydroxyindole-2-
carboxylic acid)
1. Partially soluble in strong
alkali
2. Lighter black/ brown.
• Has a good shielding property
against UV radiation
• Scavenges UV-induced
reactive oxygen species.
Pheomelanin
• Yellow/orange
• Complex macromolecule
formed by oxidation and
polymerization of sulphur-
containing cysteinyldopa
• Highly soluble in alkali
• Has poor shielding property
• Acts as a pro-oxidant.
12. Melanosomes
• Melanosomes are round to oval shaped
lysosome-related organelles that exist only in
melanocytes and retinal pigment epithelium
• They are the main sites of synthesis and storage
of melanin.
• Melanosome containing
– Eumelanin – Eumelanosomes.
– Pheomelanin - Pheomelanosomes
20. PHOTOBIOLOGY
• Photobiology is the study of the effects of UV and
visible radiation on life and on normal skin.
• UV and visible radiation comprises a very small part
of the electromagnetic radiation spectrum.
21. • Radiation is the energy released during the
transition of a molecular electron from a higher
energy outer orbit to a less energetic inner one.
• Each such emission known as a photon, is a discrete
oscillating electromagnetic pulse of
– Energy (E)– Joules
– Wavelength (λ) – nanometers
– Velocity (c) – 3 x 108 m/s
• 𝐸 = ℎ𝑐/λ
h is Planck’s constant = 6.63 x 10-34 J/sec
22. • Energy – ability to do work (Joules)
• Power – rate of flow of energy (Watt = J/sec)
• Irradiance – rate at which light energy is
delivered to a unit area
(Power/cm2 = J/sec/cm2)
• Radiant exposure – total amount of light
delivered to the skin
Radiant exposure=Irradiance x time
23. SOURCES OF UVR
• Terrestrial UVR
– Stratospheric zone(O3) absorbs all of UVC and attenuates
UVB , with no effect on UVA.
– UVB is most intense when the sun is directly overhead.
– Solar irradiance increases with altitude.
– Vast majority of solar UVR is UVA (>90%)
24. Factors influencing skin exposure to
UV rays
• Time of the day
• Season
• Latitude
• Altitude
• Presence of particulate matter
28. Principles of interaction of EM
radiation with skin
• Photophysical reaction
– Penetration of UVR into
epidermis
– Photoexcitation of
chromophores
• Photochemical reaction
– Formation of
photoproducts
• Photobiological reaction
– Biochemical and cellular
effects.
29. Grotthuβ – Draper law
• Light must first be absorbed
by a chemical substance for
a photochemical reaction
to take place.
• A compound that absorbs
radiation is called a
Chromophore
• Eg. DNA, trans-uronic acid,
proteins with aromatic
amino acids, melanin,
porphyrins, flavin
30. Response of chromophore
• Following absorption of energy, the electrons are
raised to a higher orbit called Photoexcitation.
• Upon photoexcitation, a photochemical reaction
occurs to form a new different molecule,
Photoproduct.
• Eg. Previtamin D3 is a photoproduct of
photoexcited 7-dehydrocholesterol.
31. Stokes law
• Sometimes, instead of forming a
photoproduct, the excited chromophore can
also return to its ground state with the release
of energy as heat or emission of a photon as
fluoresence.
• The wavelengths of fluoresence is always
longer(less energetic) than the exciting
wavelength.
32. • Measurement of UV radiation accurately is
called Dosimetry.
• 2 types of dosimetry
– Physical dosimetry: contain sensors, typically
photodiodes that respond to particular
wavebands
– Biological dosimetry: skin acts as a sensor.
• Minimal erythema dose(MED) – most widely used
measurment .
• Standard erythema dose(SED)
33. Action spectroscopy
• An action spectrum
(wavelength dependent)
determines the relationship
between the wavelength and
photobiological outcome.
• The spectrum for erythema in
normal skin demonstrates that
UVB in orders of magnitude is
more erythemogenic than
UVA for a given UVR dose.
• Purpose of action
spectroscopy
35. DNA photodamage
• Cellular epidermis is rich in UVR absorbing
chromophores , the most important being DNA.
• Pyrimidine dimers are formed as photoproducts
– Cyclobutane pyrimidine dimer (CPD)
– 6-4 pyrimidine-pyrimidone
• They are regulated by p53
37. Base excision repair(BER)
DNA glycosylases recognize and remove damaged
bases
Apurinic/apyrimidic site(AP site)
Single strand break is processed by either short-
patch BER
Or long-patch BER
38. • Formation of epidermal sunburn cells
– Sunburn cells are apoptotic keratinocytes that are
readily induced by UVB but not by UVA1.
– The cells have a pyknotic nuclei and eosinophilic
cytoplasm
• Loss of langerhans cell dendricity and number
– This is accompanied by epidermal spongiosis, dermal
vasodilation,neutrophil and CD3+ infiltration.
• Skin hyperplasia
– Particularly of the stratum corneum
– Hours to days after UVB exposure
39. Acute clinical effects of UVR
• Reactions that occur within seconds to weeks
after a single UVR exposure.
40. ERYTHEMA –
• is UVR induced inflammation.
• It is apparent after about 6 hours and peaks
at about 24 hours and gradually resolves over
a few days.
• It may be associated with pain, warmth,
oedema in severe cases.
• Wavelengths around 300nm (UVB) are the
most DNA damaging and also erythemogenic
41. TANNING
– IMMEDIATE PIGMENT DARKENING (IPD)
• Presents as a transient grey colour which is due to
immediate photo-oxidation of existing colourless melanin
precursors.
• It fades within 15 mins
• Induced by low UVA doses(1-4 J/cm2)
• Not protective against erythema
– PERSISTENT PIGMENT DARKENING(PPD)
• It is a brown colour formation in response to higher UVA
doses (>10J/cm2)
• Peaks 2 hours post-irradiation and lasts for 1-5 days
• It is due to persistent oxidation of melanin precursors
• PPD is an end point used to assess UVA protection of
sunscreens.
42. – DELAYED TANNING (DT) OR MELANOGENESIS
• There is stimulation of new melanin synthesis by basal
epidermal melanocytes , which is transported via
dendrites to adjacent keratinocytes.
• Eumelanin protects 2-3 times against DNA
photodamage and erythema.
• It is evident after 3 days of irradiation.
• Tan fades when stratum corneum is shed over several
weeks.
43. FITZPATRICK’S
SKIN TYPE
SUN BURN RISK TANNING ABILITY SKIN CANCER
RISK
1 ++++ +/- HIGH
2 +++ + HIGH
3 ++ ++ MODERATE
4 + +++ MODERATE
5 +/- ++++ LOW
6 +/- ++++ LOW
44. • VITAMIN D
PRODUCTION
– It is the only
established benefit of
solar UVR exposure.
– Chromophore – 7-
dehydrocholesterol
(pro-vitaminD)
– It is converted to pre-
vitamin D by UVB
action spectrum.
– There is no evidence of
UVA involvement in
vitamin D production.
– Darker skin types have
poorer vit D status
45. • IMMUNOMODULATION
– Pro-inflammatory properties
• Sunburning, inflammatory dermatoses, triggering of
autoimmune connective tissue diseases
• Mediated by innate immunity
• Release of mediators like serotonin, prostaglandins, IL-1,6,8,
TNF-a
– Anti-inflammatory properties
• Reactivation of herpes labialis, efficacy of phototherapy in
treatment of inflammatory dermatosis
• Mediated by migration of langerhans cells from epidermis to
lymph nodes
• Release of mediators like IL-10, a-MSH
• Induction of antigen-specific regulatory T-cells.
46. • CARDIOVASCULAR EFFECTS
– A single suberythemal dose of UVA (320-400 nm)
can lower BP via the release of nitric oxide from
the skin into the systemic circulation.
47. CHRONIC CLINICAL EFFECTS OF UVR
• SKIN CANCER
– Keratinocyte cancer – basal cell ca, squamous cell carcinoma
– Melanocyte cancer – malignant melanoma
– Actinic keratosis (risk for SCC)
• PHOTOAGEING
– Characterized by fine and course wrinkling, dryness, coarseness,
telangiectasia, yellowness and irregular patchy pigmentation.
– Loss of mechanical properties of skin due to collagen and elastin
degradation.