Flashcards in Exam 1 Koh- Cornea Biochem 2 Deck (98):
What are the types of collagen in the basal lamina?
4, 7, 9, 16
What 3 things are included in the basal lamina?
Collagen, fibronectin, Heparan sulfate
What proteoglycans are included in the stroma?
Keratan sulfate, dermatan sulfate, chondroitan sulfate
What types of collagen are in the stroma?
1 and 6 (major), 3 and 5 (minor)
What 3 things included in Descemet's membrane?
Collagen, laminin, fibronectin
What types of collagen are in Descemet's membrane?
4 and 8
What are MMPs?
A family of Zn2+ dependent enzymes
What do MMPs do?
Degrade ECM components (proteoglycans/collagens)
How many members of MMPs? What is found in a healthy cornea?
>26 members, only MMP2 found in healthy cornea
What MMPs are synthesized after corneal injury?
MMP1, MMP3 and MMP9
What is the physiological function of MMPs?
Neurite growth, cell migration, would healing, vessel growth, ovulation
What is the pathological function of MMPs?
Tumor growth and migration, fibrosis, glaucoma, arthritis, lupus, etc.
What are MMP substrates?
Most of the ECM components (fibronectin, vitronectin, laminin, entactin, tenascin, aggrecan, myelin, basic protein, etc.) and collagens (1, 2, 3, 4, 5,6, 7, 8, 9, 10, 14)
What are the tissue inhibitors of metallo proteinases?
TIMP 1-4, differentially expressed in tissues, and temporally follow the influx of MMPs, TIMP-2 is constitutively produced as is MMP-2
What are keratocytes?
Major cell type of the stroma and are involved in maintaining the ECM environment
What are some stromal problems?
Granular dystrophy, keratoepithelin (ECM, adhesion differentiation), lattice dystrophy, herpetic stromal keratitis
How think is Descemet's membrane?
~10 micrometers thick
What secreted Descemet's membrane?
What type of collagen is most abundant in Descemet's membrane?
What collagens are included in Descemet's membrane?
4, 5, 8, 9, 12
What is the function of Descemet's membrane?
Provides elasticity and deformability, imparts strength and resilience, the main resistance to normal intraocular pressure
What are 2 Descemet/Endothelial Problems?
Vogt's striae, decreased central corneal thickness
What type of cells are in the endothelium?
Polygonal cells 20 micometers in diameter
What is the cell density in the endothelium?
About 3000/ mm^2
What type of junctions are in the endothelium?
What do the pumps do in the endothelium?
Maintain a partially dehydrated state
What happens to the endothelium in aging?
Endothelial cells decreases with aging, a concomitant spreading and thinning of the remaining cells
Where is water pumped into?
What type of aquaporin is in the epithelium?
What type of aquaporin is in the endothelium?
Oxygen from the _____ _____ for aerobic glycolysis
What type of antiport is in the cornea?
Na+/H_ antiport: Na+ (in) with H+ (out), maintain intracellular pH
What are 2 pumps in the cornea?
Na+ movement (tears -> epithelium), passive diffusion; Na+ movement (epithelium -> stroma) active Na+/K+ ATPase
How does transport of fluid occur in the cornea?
Transport of fluid out of the cornea (HCO3-/Cl- pump), outward extrusion of Cl-, inward transport of Na+ and HCO3-
What is corneal transparency due to?
Individual fibrils are ineffective scatterers because of their small diameter and their refractive index is relatively close to the surrounding ground substance, destructive interference, cornea is thin and avascular
What does destructive interference do?
Reduces the scattering by a factor of ~10 over that which would occur if the fibrils scattered independently of one another
What percentage of the cornea is hydrated?
What percentage of the sclera is hydrated?
The corneal stoma ____ water
How do GAGs contribute to hydration?
What is the cornea analogous to?
A slice of water stabilized in 3D by a meshwork of fibrils and soluble polymers
What can cause corneal swelling?
Abrasion, high IOP, swelling pressure is > metabolic pump rate
Swelling pressure generates a level of ____ ____
Swelling disrupts normal ___ arrangement
Contact lens effects are predominantly affect the function of the ______
What are 4 CLs effects?
CLs shift from aerobic to anaerobic metabolism, lactate levels in the cornea are doubled with CL wear, induced stromal acidosis impairing deturgescence, neovascularization
What does the epithelium receive oxygen from?
The epithelium receives glucose from the circulation via the _____
What are the factors underlying transparency loss in the edematous cornea?
Increased light scattering, disordered fibrillar distributions and regions "lakes" where fibrils are missing, lakes would cause large fluctuations in the refractive index, increasing light scattering
How does the corneal epithelium regenerate?
Constantly regenerates by mitotic activity in the basal layer of cells at the limbus
Aster injury to the epithelium, there is migration of a single-cell layer across the _____ to close the defect
What reforms in epithelial repair?
Hemidesmosomes and intercellular contacts
In epithelial repair, single cell layer is restored to a ___ layered architecture
What is migration in epithelial healing?
Marked cytoskeletal and cell shape changes involving redistribution of actin-myosin fibrils
Intracellular signaling via ___ ___ ____
Cell surface integrins
How does the epithelium adhere to the BM and Bowman's layer?
Many _____ elapse before anchoring fibrils reappear in adhesion
Many _____ pass before full ultrastructural integrity is restored
Recurrent Corneal Erosion
Damage to the superficial stromal layers
How does stromal repair occur?
Immediate imbibition of water from the tears by the GAGs, causes localized opacification (light scatter), initiates deposition of fibrin within the wound, rapid epithelialization of the wound incision, and finally activation of the keratocytes to divide and synthesize collagen and GAGs
Irregular size and arrangement of fibrils
In extensive wounds, there is _____ opacification
What are the stages of stromal wound healing
After wounding, transparent keratocytes differentiate into migratory fibroblasts, fibroblasts migrate into the wound margin, at the wound margin fibroblasts differentiate into nonmotile, contractile myofibroblasts, after wound closure, myofibroblasts disappear
Every 10 micrometers in LASIK and PRK is equal to how many diopters of myopia?
For hyperopia, the anterior stromal tissue in LASIK and PRK is removed from the _____
What are characteristics of PRK-induced haze?
Corneas frequently develop anterior light scattering that causes a hazy appearance following photorefractive keratectomy, variable levels of collagen 4 after surgery; rate of re-epithelialization; keratocyte apoptosis; and relationship between TGF-beta and myofibroblast transformation
PRK-induced haze peaks when?
2-6 months postsurgery in humans, after which it diminishes
What are the 3 unhealed wounds of LASIK?
Small flap scar, weak flap, eye banks reject
What are some advantages of Small Incision Lenticule Extraction (SMILE)?
Simple, all femtosecond procedure; no tissue ablation; environmental conditions do not affect treatment outcomes; no flap-related risks; enables correction of higher myopia; low impact on corneal nerves, less postop "dry eye" than LASIK; preserves strong anterior stromal tissue; less biomechanical impact; flap-less minimally invasive "keyhole" procedure attractive to patients
What is the future of SMILE?
Lenticule profiles for hyperopia, presbyopia, and custom (wavefront-or topography-guided) correction; inserting donor lenticules into corneal pockets for refractive correction
What is the corneal wound healing cascade for a clear eye?
Epithelial injury -> keratocyte apoptosis -> keratocyte proliferation and migration -> Normal basement membrane regeneration -> NO myofibroblast generation
What is the corneal wound healing cascade for a hazy eye?
Epithelial injury -> keratocyte apoptosis -> keratocyte proliferation and migration -> inflammatory cell infiltration -> defective basement membrane regeneration -> myofibroblast generation
Endothelial repair does not undergo ____ in humans
What happens to the endothelium with age?
A decline in number, an increase in size and variable morphology, cornea imbibes water (decompensates) and becomes opaque
Normal corneal endothelium has no type___ collagen, after injury, fibroblastic cells express type ___ collagen
What is the immune privilege of the cornea?
Devoid of both blood and lymphatic vessels, TGFb
What compounds are anti-angiogenesis in the cornea?
PEDF, thrombospondin, angiostatin, endostatin, soluble VEGFR1
What compounds are pro-angiogenesis in the cornea?
VEGF, hypoxia inducible factor-1alpha, interleukin-8, tumor necrosis factor-alpha, angiogenin
What is interleukin-1?
A master regulator that stimulates keratocytes to secrete secondary cytokines
What are 3 reasons vascularization occurs?
Injury, infection, contact lens wear (20-30%)
What are types of infiltrates?
Neutrophils, basophils, eosinophils, monocytes, lymphocytes, RBCs, Langerhans cells
What 3 entities affects corneal transparency?
Inflammation, neovascularization, endothelial pums
A deficiency in vitamin A leads to what?
Impaired cornea and conjunctial epithelial function, loss of goblet cells in the conj, 'keratinization' of the corneal epithelium, corneal opacity, Bitot's spots, punctate erosions, xerophthalmia
What commonly gathers in the epithelium?
When does a horizontal Hudson-Stahli line form?
After 50, iron
What is the Fleischer ring?
Peripheral rings in the cornea made of iron, 50% keratoconus
What is the Stocker line?
Iron deposition, in the epithelium ahead of pterygium
What is Ferry's line?
Corneal epithelium iron line at the edge of filtering blebs
What is Kayser-Fleischer ring made of?
Within Descemet's membrane, there is a pigmented copper ring at the periphery of the cornea in ____ _____
How do you get silver and gold deposition in the cornea?
After prolonged topical application of silver-containing eye drops, prolonged gold therapy for RhA
What are oxidative products?
Superoxide, H2O2, free radicals
What are ocular effects of oxidative damage?
Actinic keratosis, pingueculum, pterygium, endothelial changes, age-related cataract
What is the tear film made of?
Mucins, superoxide dismutase, ascorbic acid, glutathione, Cys, Tyr, uric acid
What antioxidants is the aqueous humor made of?
Cys, AA, GSH (glutathione), UA, Tyr
What antioxidants is the lens made of?
Cys, AA, GSH, UA, Tyr
What happens to the cornea in diabetes?
Altered tear chemistry, decreased corneal sensitivty, increased epithelial fragility, corneal thickened, endothelial polymegathism, slower wound healing, long-term contact lens wear