Day 4 (1): Anatomy and Physiology of the Lens and Cataract Flashcards
What is the crystalline lens?
Between the aqueous humor and the vitreous body
Transparent
Functions:
1. Transmission and focusing of light towards retina
2. Accommodation
(+) CAPSULE: acellular and elastic
Discuss the embryology of the crystalline lens.
4 weeks AOG
4 mm: (+) LENS PLACODE: thickening of the surface ectoderm induced by optic vesicle –> invaginates –>
5 mm: (+) LENS PIT –> encloses and separates from ectoderm –>
9-10 mm: (+) LENS VESICLE
(+) OPTIC VESICLE –> invagination –> OPTIC CUP
5 weeks AOG (16 mm):
(+) PRIMARY Lens Fibers: elongation of POSTERIOR cells anteriorly with nuclei loss + obliteration of cavity –> EMBRYONIC NUCLEUS
6 weeks AOG (20 mm):
(+) Lens Capsule
(+) Basal Lamina
(+) Tunica Vasculosa Lentis: vascular system from Hyaloid Artery
7 weeks AOG (25 mm):
(+) SECONDARY Lens Fibers: elongation and division of ANTERIOR cells in the EQUATORIAL zone –> FETAL NUCLEUS
8 weeks AOG (35 mm):
(+) SUTURE Lines
10 weeks AOG (40 mm):
Well-developed Tunica Vasculosa Lentis
3 months (65 mm):
(+) Zonular lamella: suspensory ligaments of lens formed from neuroepithelium –> attaches capsule to inner surface of CB
(+) Uvea (CB and Iris): from the optic vesicle
4 months (110 mm):
Well-developed zonules
Regression of hyaloid system STARTS
6 months (240 mm):
Regression of pupillary membrane
8-9 months/Birth:
Regression of hyaloid system COMPLETED –> AVASCULAR
Throughout life:
Formation of ADULT NUCLEUS and CORTEX
Remember
1. CENTRAL ANTERIOR epithelial cells do NOT divide
2. EQUATORIAL epithelial cells is the MITOTIC zone
3. OLDER cells are displaced towards CENTER, becoming more dense –> LENS NUCLEUS (embryonic + fetal + adult)
3. YOUNGER, SUPERFICIAL cells from equatorial zone elongates and moves centrally –> LENS CORTEX
What are suture lines?
Represent junctions between the tips of the lens fibers that make up the lens cortex as they elongate anteriorly under the undifferentiated epithelium and posteriorly beneath the posterior capsule from the equator.
Anterior: upright “Y”
Posterior: inverted “Y”
Describe the structure of the crystalline lens.
Biconvex
Transparent
Colorless in young, Yellow to Brown with aging
Completely enclosed in the CAPSULE
Held in place by ZONULES (suspensory ligaments)
AP diameter thickens with age ~ 0.02 mm/year
- NB: 3.5 mm
- Elderly: 5.0 mm
EQUATORIAL diameter: increase slows down at age 15 (9.0 mm)
ANTERIOR surface is FLATTER (larger radius of curvature)
POSTERIOR surface more CURVED (smaller radius of curvature)
Note:
Radius of Curvature: radius of a circle that best fits the arc
Describe the anatomy of the crystalline lens.
Parts:
- CAPSULE
- Transparent, elastic, acellular and fibrillar
- Thicker ANTERIORLY
- Avoid rupturing thinner POSTERIOR capsule during surgery
- Zonular lamella: denser outer layer where zonules attach
- Type IV collagen + 10% GAGs
- Basement membrane of epithelial cells
- (+) PAS: stains carbohydrates - EPITHELIUM
- Single layer of cells beneath the anterior and equatorial region
- NONE in the posterior region
- Cuboidal to columnar
- Base: facing the capsule
- Apex: facing the cortex - FIBER CELLS
- Majority of lens
- Hexagonal
- Ends meet at the SUTURE lines - CYTOSKELETON
- Structural integrity, cell mobility and fiber elongation
- Filaments, Microfilaments, Microtubules
Describe the composition of the crystalline lens.
Optimized for optical function
- Water: 2/3 (relatively LOW vs other tissues)
- Refractile Proteins: 1/3 (relatively HIGH)
- Others (lipids, ions, metabolites): 1-2%
Water:
- Concentrated in the softer cortex vs denser nucleus
- Hydration NOT altered with aging
- Precisely regulated –> transparency
- Alterations in water content (cell swelling, shrinkage or inc. EC space) –> distortion of architecture –> light scatter –> BOV
Proteins:
- Relatively higher vs other tissues
Discuss protein composition of the lens.
Synthesis: epithelium and superficial cortex
- affected by inhibition and lack of building blocks
2 general groups:
Crystallins: water-soluble
Non-Crystallins: water-insoluble
Crystallins: increase and precipitation causes opacification
- Alpha: 30%; 4 subunits
- Beta: 54% (most aBundant)
- Gamma: 16% (least)
Non-Crystallins
Membrane Proteins: 20-30%
- Intrinsic: part of gap junctions
- Extrinsic: in other tissues (fibronectin)
Enzymes: cell membranes
- Na-K-ATPase, Alkaline phosphatase, Adenyl cyclase
Glycoproteins: membrane receptors, cell signaling and recognition
- Glyco = mostly Galactose
Cytoskeleton: structural integrity
- Actin: beta and gamma forms
- Vimentin: intermediate
Describe the physiology and biochemistry of the lens.
pH: 6.90 (close to normal)
- (+) intrinsic buffering capacity
- Amino acids: actively-transported
- Glucose: primary energy source
- Fructose, Glycogen, Sorbitol also present
- Fuel for solute transport, mitosis, and lipid and protein synthesis
- Note: capable of aerobic (Kreb’s), anerobic (glycolysis), HMP or Sorbitol pathway - Lipids: found in cell membranes
- Cholesterol, phospholipids (sphingomyelin), glycosphingolipids (ceramide + carbohydrate)
- Cell membrane integrity and signaling
- Fiber cell formation - Ascorbic Acid: HIGH
- TRANSPORTED from aqueous humor
- Antioxidant scavenger of ROS - Glutathione: HIGH
- SYNTHESIZED by lens
- Antioxidant scavenger of ROS
- Maintains membrane permeability and transport mechanisms
- Maintains proteins in reduced state
- Loss –> oxidized state due to ROS –> cross-linkage –> aggregation –> opacification - Inositol and Taurine: precursor of membrane components
What is cataract?
Loss of transparency or the opacification of the lens leading to decreased VA and impairment
Increasing incidence with age (70% in 65 yo, 90% in 75 yo)
DISORGANIZED lens structure
1. Swollen and degenerated structure
2. Aberrant epithelial morphology
3. Altered cell surfaces
Changes in the lens with aging.
- Lens WEIGHT and VOLUME increase
- COLOR: transparent –> white opaque –> yellow –> amber
- Protein synthesis and other metabolic processed HALTED
- Less malleable –> decreased accommodation
What is the Chylack Classification or the Lens Opacification Classification System?
LOCS III
- Describes opacity based on LOCATION and COLOR
- Location: Nuclear, Cortical or Posterior Subcapsular
- Color: compared to standard image
- Severity: graded on a decimal scale,
- 6 slit-lamp images for grading NUCLEAR color (NC) and nuclear opalescence (NO)
- 5 retroillumination images for grading CORTICAL cataract (C)
- 5 retroillumination images for grading POSTERIOR SUBCAPSULAR (P) cataract.
What is senile cataract?
Mature-onset cataract
Most common type
Occurs with aging
Altered protein, membrane and lipid physiology and biochemistry
NUCLEAR: impaired MEMBRANE permeability
CORTICAL: ELECTROLYTE and WATER imbalance
Relationship between oxidative damage and cataractogenesis.
Reactive Oxygen Species:
- Sulfhydryl groups of proteins must remain in a REDUCED state
- Oxidizes proteins causing crosslinking, aggregation and opacification
- Superoxide
- Hydrogen peroxide
- Hydroxide
Glutathione: antioxidant which scavenges and inactivates ROS
Relationship between calcium levels and cataractogenesis.
Increased Ca levels –> Opacification via:
1. DECREASED glucose metabolism –> increased glucose in lens
2. CALMODULIN activation
Relationship between UV light and Ionizing Radiation and cataractogenesis.
UV Light
- Damages lens proteins
- Excessive light exposure –> Cataracts
Ionizing Radiation
- X-rays, Gamma rays, Beta particles
- Causes structural changes –> POSTERIOR SUBCAPSULAR
- DOSE-dependent
