Exam 1 Koh- Cornea Biochem 2 Flashcards
1
Q
What are the types of collagen in the basal lamina?
A
4, 7, 9, 16
2
Q
What 3 things are included in the basal lamina?
A
Collagen, fibronectin, Heparan sulfate
3
Q
What proteoglycans are included in the stroma?
A
Keratan sulfate, dermatan sulfate, chondroitan sulfate
4
Q
What types of collagen are in the stroma?
A
1 and 6 (major), 3 and 5 (minor)
5
Q
What 3 things included in Descemet’s membrane?
A
Collagen, laminin, fibronectin
6
Q
What types of collagen are in Descemet’s membrane?
A
4 and 8
7
Q
What are MMPs?
A
A family of Zn2+ dependent enzymes
8
Q
What do MMPs do?
A
Degrade ECM components (proteoglycans/collagens)
9
Q
How many members of MMPs? What is found in a healthy cornea?
A
> 26 members, only MMP2 found in healthy cornea
10
Q
What MMPs are synthesized after corneal injury?
A
MMP1, MMP3 and MMP9
11
Q
What is the physiological function of MMPs?
A
Neurite growth, cell migration, would healing, vessel growth, ovulation
12
Q
What is the pathological function of MMPs?
A
Tumor growth and migration, fibrosis, glaucoma, arthritis, lupus, etc.
13
Q
What are MMP substrates?
A
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)
14
Q
What are the tissue inhibitors of metallo proteinases?
A
TIMP 1-4, differentially expressed in tissues, and temporally follow the influx of MMPs, TIMP-2 is constitutively produced as is MMP-2
15
Q
What are keratocytes?
A
Major cell type of the stroma and are involved in maintaining the ECM environment
16
Q
What are some stromal problems?
A
Granular dystrophy, keratoepithelin (ECM, adhesion differentiation), lattice dystrophy, herpetic stromal keratitis
17
Q
How think is Descemet’s membrane?
A
~10 micrometers thick
18
Q
What secreted Descemet’s membrane?
A
Endothelium
19
Q
What type of collagen is most abundant in Descemet’s membrane?
A
4
20
Q
What collagens are included in Descemet’s membrane?
A
4, 5, 8, 9, 12
21
Q
What is the function of Descemet’s membrane?
A
Provides elasticity and deformability, imparts strength and resilience, the main resistance to normal intraocular pressure
22
Q
What are 2 Descemet/Endothelial Problems?
A
Vogt’s striae, decreased central corneal thickness
23
Q
What type of cells are in the endothelium?
A
Polygonal cells 20 micometers in diameter
24
Q
What is the cell density in the endothelium?
A
About 3000/ mm^2
25
What type of junctions are in the endothelium?
Tight
26
What do the pumps do in the endothelium?
Maintain a partially dehydrated state
27
What happens to the endothelium in aging?
Endothelial cells decreases with aging, a concomitant spreading and thinning of the remaining cells
28
Where is water pumped into?
Aqueous humor
29
What type of aquaporin is in the epithelium?
5
30
What type of aquaporin is in the endothelium?
1
31
Oxygen from the _____ _____ for aerobic glycolysis
Aqueous humor
32
What type of antiport is in the cornea?
Na+/H_ antiport: Na+ (in) with H+ (out), maintain intracellular pH
33
What are 2 pumps in the cornea?
Na+ movement (tears -> epithelium), passive diffusion; Na+ movement (epithelium -> stroma) active Na+/K+ ATPase
34
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-
35
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
36
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
37
What percentage of the cornea is hydrated?
80
38
What percentage of the sclera is hydrated?
70
39
The corneal stoma ____ water
Imbibes
40
How do GAGs contribute to hydration?
Hydrophilic
41
What is the cornea analogous to?
A slice of water stabilized in 3D by a meshwork of fibrils and soluble polymers
42
What can cause corneal swelling?
Abrasion, high IOP, swelling pressure is > metabolic pump rate
43
Swelling pressure generates a level of ____ ____
Interfibrillar tension
44
Swelling disrupts normal ___ arrangement
Fibril
45
Contact lens effects are predominantly affect the function of the ______
Epithelium
46
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
47
What does the epithelium receive oxygen from?
Tears
48
The epithelium receives glucose from the circulation via the _____
Aqueous
49
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
50
How does the corneal epithelium regenerate?
Constantly regenerates by mitotic activity in the basal layer of cells at the limbus
51
Aster injury to the epithelium, there is migration of a single-cell layer across the _____ to close the defect
Stroma
52
What reforms in epithelial repair?
Hemidesmosomes and intercellular contacts
53
In epithelial repair, single cell layer is restored to a ___ layered architecture
6
54
What is migration in epithelial healing?
Marked cytoskeletal and cell shape changes involving redistribution of actin-myosin fibrils
55
Intracellular signaling via ___ ___ ____
Cell surface integrins
56
How does the epithelium adhere to the BM and Bowman's layer?
Hemidesmosomes
57
Many _____ elapse before anchoring fibrils reappear in adhesion
Days
58
Many _____ pass before full ultrastructural integrity is restored
Months
59
Recurrent Corneal Erosion
Damage to the superficial stromal layers
60
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
61
Opacity
Irregular size and arrangement of fibrils
62
In extensive wounds, there is _____ opacification
Irreversible
63
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
64
Every 10 micrometers in LASIK and PRK is equal to how many diopters of myopia?
1
65
For hyperopia, the anterior stromal tissue in LASIK and PRK is removed from the _____
Periphery
66
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
67
PRK-induced haze peaks when?
2-6 months postsurgery in humans, after which it diminishes
68
What are the 3 unhealed wounds of LASIK?
Small flap scar, weak flap, eye banks reject
69
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
70
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
71
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
72
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
73
Endothelial repair does not undergo ____ in humans
Mitosis
74
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
75
Normal corneal endothelium has no type___ collagen, after injury, fibroblastic cells express type ___ collagen
1, 1
76
What is the immune privilege of the cornea?
Devoid of both blood and lymphatic vessels, TGFb
77
What compounds are anti-angiogenesis in the cornea?
PEDF, thrombospondin, angiostatin, endostatin, soluble VEGFR1
78
What compounds are pro-angiogenesis in the cornea?
VEGF, hypoxia inducible factor-1alpha, interleukin-8, tumor necrosis factor-alpha, angiogenin
79
What is interleukin-1?
A master regulator that stimulates keratocytes to secrete secondary cytokines
80
What are 3 reasons vascularization occurs?
Injury, infection, contact lens wear (20-30%)
81
What are types of infiltrates?
Neutrophils, basophils, eosinophils, monocytes, lymphocytes, RBCs, Langerhans cells
82
What 3 entities affects corneal transparency?
Inflammation, neovascularization, endothelial pums
83
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
84
What commonly gathers in the epithelium?
Iron
85
When does a horizontal Hudson-Stahli line form?
After 50, iron
86
What is the Fleischer ring?
Peripheral rings in the cornea made of iron, 50% keratoconus
87
What is the Stocker line?
Iron deposition, in the epithelium ahead of pterygium
88
What is Ferry's line?
Corneal epithelium iron line at the edge of filtering blebs
89
What is Kayser-Fleischer ring made of?
Copper
90
Within Descemet's membrane, there is a pigmented copper ring at the periphery of the cornea in ____ _____
Wilson's disease
91
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
92
What are oxidative products?
Superoxide, H2O2, free radicals
93
What are ocular effects of oxidative damage?
Actinic keratosis, pingueculum, pterygium, endothelial changes, age-related cataract
94
What is the tear film made of?
Mucins, superoxide dismutase, ascorbic acid, glutathione, Cys, Tyr, uric acid
95
What antioxidants is the aqueous humor made of?
Cys, AA, GSH (glutathione), UA, Tyr
96
What antioxidants is the lens made of?
Cys, AA, GSH, UA, Tyr
97
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
98
What are the age-related changes in the cornea?
Thickening of epithelial basement membrane, decrease in nerve density, decrease in stromal cell density, thickening of Descemet's membrane, appearance of Hassall-Henle Bodies, decrease in number of corneal endothelial cells
