4. Ocular Ageing and Histopathology Flashcards
(36 cards)
All biological tissues will eventually fail even if optimally maintained. Most are expected to expire by 120 years. They expire due to genetic and environmental factors. This pushes their limit to regenerate.
Which 5 places are considered Blue Zones? What does that mean?
Blue Zones are places with longer lifespans.
* Island of Sardinia, Itay
* Okinawa, Japan
* Loma Linda, California
* The Nicoya Peninsula, Costa Rica
* Ikaria, Greece
What are the 9 cellular consequences of aging?
- Inflammation
- Altered intracellular communication
- Cellular senescence
- Telomere attrition
- Epigenetic alterations
- Mitochondrial dysfunction
- Loss of proteostasis
- Deregulated nutrient sensing
- Stem cell exhaustion
When do cells become under stress?
When balance between injury and repair is disrupted. If cell dies faster than replaced, the remaining cells are placed under stress.
What help control the balance betweeen injury and repair?
Extracellular and intracellular factors control cell division and apoptosis.
What are the 2 main theories of aging?
- Free radical theory - mitochondria as source of oxidative stress with aging
- Replicative senescence - incomplete telomere duplication with each cell division, help prevent proliferation of damage
What triggers cellular senescence? (3)
- Damage - poor nutrition, high fat/ salt, raidation (UV), smoking, stress
- DNA damage - epigenetic modification
- Repair, clearance, cell renewal
What are the 3 things that cellular senescence will trigger?
- More damaged cells
- Pro-ageing → reduced function, inflammation on adjacent cells, stem cell exhaustion
- Disease
Interactions between age-related damage & repair
* Reduced replication capacity → telomeres shorten with subsequent mitoses; exhaustion of stem cells
* Damage by increased external reactions → increasing advanced glycation end-products (AGEs); UV exposure promotes protein crosslinking
* Tissue dysfunction due to exaggerated normal interactions → progressive deposition of cholesterol/ lipid on elastin = reduces elasticity of blood vessels
* Altered gene expression → increased expression of genes for inflexible elastin
* Less efficient mitochondria due to accumulation of mtDNA damage → reduced ATP & increases free radical production
* Reduced intracellular recycling = autophagy, mitophagy → cells cannot eliminate abnormal byproducts, used mitochondria can’t recycle components
Which 9 conditions increase in prevalence with aging?
- Presbyopia
- Floaters
- Dry eyes/ tearing
- Cataracts
- Glaucoma
- Retinal disorders: AMD, DR, detached retina (vitreous liquefaction)
- Conjunctivitis
- Eyelid problems
- Temporal arteritis
Name the conditions that cause significant visual impairment in Australians aged 55 or more (from highest to lowest prevalence).
- Cataract (40%)
- AMD (28%)
- Glaucoma (8%)
- Diabetic retinopathy (4%)
- Others
What is the major risk factor for vision loss?
Ageing - over 55 years of age
Age-related cataract is the most common ocular pathology encountered by eye care practitioners.
3 forms often occur togehter
* Nuclear (milky-yellow)
* Anterior cortical (spokes, wedges)
* Posterior subcapsular
What are the 3 major causes of nuclear cataract?
- Lens fibre compaction
- Increased density of nucleus → lens turns milky or yellow (brunescence); myopic shift
- Reflective crystalline deposits → glare
What are the consequences of nuclear cataract in terms of having a dense nucleus? (4)
Dense border between cortex and nucleus creates a barrier for O2 and antioxidant transport
* Decrease O2 flow to nucleus
* Oxygen pools at nucleus edge = increase oxidative stress
* Decrease antioxidant access (glutathione) to nucleus
What are the consequences of UV exposure to the lens?
- UV exposure generates oxygen free radicals
- Lens crystallin reacts with free radicals
- Causing protein aggregation → truncation, glycation, unfolding → unstable crystallins → large aggregates
- Loss of solubility → covalent bonds crosslinking between crystallins; precipitate into protein-rich and protein poor regions, crystallisation
How does cortical cataract form? (4 points)
UV and stress induces fibre fragmentation
* Fragmented fibres and protein form globules
* Sulphydryl bonds crosslinking of proteins promotes folding and aggregation to form globules
Liquefied cells form ‘clefts’ or channels in lens
* Protein accumulation → osmotic gradient → draws water & pool along past fibre channels
* Can cause astigmatic and hyperopic shifts
What are the causes of posterior subcapsular cataract? (4)
- Radiation exposure
- Age
- Toxic damage (e.g. systemic corticosteroids)
- Secondary to eye diseases (e.g. uveitis, retinitis pigmentosa, diabetes)
Posterior Subcapsular Cataract
Early changes
* Localised vacuoles
* RI reduction
Later changes
* Epithelial cell migration from equator, converge at posterior pole, form bladder cells of Wedl and new basement membrane
* Cell organelles, cell clumps, basement membrane scatter light
* Dramatic reduction in vision because centrally positioned near nodal point
Vitreous liquefaction occurs in healthy aging. It is often innocuous and can lead to posterior vitreous detachment in 65% of people over the age of 65.
Damages to the vitreal fibres, hyaluronan fibres (hydrophilic) is often caused by UV, high sugar levels or AGE. This causes collapse of fibrils, breakdown of collagen into smaller fragments and loss of gel structure with water pooling. It can also cause formation of floaters.
How is vitreous liquefaction a precursor to cataract? (3)
- Vitreous liquefaction increases oxgen tension at the lens (partial O2 pressure is lower in vitreous gel vs fluid)
- This increases oxidative stress on the lens ∵ excess O2 becomes superoxide + oxidants
- Promotes lens protein damage and crosslinking
Describe the hallmarks and appearances of wet (exudative) age-related macular degeneration.
Wet (exudative)
* hallmark = ingrowth of blood vessels
* Choroidal neovascular membrane (CNVM) → leaky leading to RPE detachment, subretinal haemorrhage
* End stage = Disciform scar formation (fibrosis)
Describe the hallmarks and appearances of dry (non-exudative) age-related macular degeneration.
Dry (non-exudative)
* hallmark = Geographic atrophy → one or more discrete areas, 1/2DD or more of loss of retina & RPE
* change in pigmentation
* hyper or hypo-pigmentation
* No treatment
What is the definition of geographic atrophy?
Loss of retina and RPE in one or more discrete areas, measuing 500μm or 0.5DD or more. They allow prominent visualisation of the choroidal vessels.
