X,Y,Z hypothesis

• X=proliferation
• Y=centripetal migration of peripheral basal cells
• Z=cell loss by desquamation

• CAM
• associated w/intracellular plaque
• in all epithelial cells (basal, wing, sq.)

• cell to ECM
• secreted by basal cells
• contiunous w/anchoring fibrils and plaques into bowmans
• constantly broken and reformed
• take a long time to resetablish following injury

• cadherins, integrins, and adherins
• cell to cell or cell to ECM
• adherins have actin in filaments which allow flexible bending of epithelial sheets

• tight jxns
• in superficial sq. cells

• corneal epith. layer
• columnar cells
• originate from stem cells at limbal epith.
• contains tonofilaments and actin
• secrete the BM (type 4 and 7 collagen)
• contains CAM's
• desmosomes, hemidesmosomes=to BM and gap jxns.

• autosomal dominant
• thickened BM w/fingerlike extentsions overlying epith.
• can result in RCE=pain upon awakening
• fibrillar material b/n BM and bowmans
• intraepithelial microcyst formed

• layer of epith.
• cuboidal w/interdigitations

• layer of epith.
• flat, polygonal, w/vacuoles
• ant. has microvilli w/glycocalyx
• desmosomes and zonula occludens

• these brkdwn jxns. and cause sloughing of outer cells
• BAK=increases perm. to NaFl
• chlorhexidine=
• EDTA=chelates Ca++ required for maintenance of tight jxns.
• all inhibit wound healing of epith
• don't use in dry eye pts.

• inflamed eye=^ proten in tears will bind to drug and decrease bioavailability
• ^ pH favor lipid solubility but decreases stability
• most drugs are ionized bases
• good pH=7.3-7.7

• basic
• undissociated form penetrates epith.
• pH in epith. dissociates to H20 soluble form to enter stroma
• small molecules pass endo.
• a surfactant can be used to breakup epith. integrity

• 78 h20
• 15 collagen
• 5 ECM

• strength of tissue determined by amount of cross linking
• variable size and interwoven
• oblique orientation ant.
• orthogonal and compacted post.
• turn and run ll at limbus

• 1=primarily in stroma, bowmans, earliest formed
• 3=stromal healing, bowmans
• 4=BM, descements
• 5, 6=stroma and bowmans
• 7=bowmans(anchoring fibrils)
• 8=descemets

• composed of proteoglycans
• proteoglycans have a leucine rich core protein bound to GAG

• KS=central cornea
• chondroitin sulfate=periph. and sclera
• dermatan sulfate=periph. and sclera, involved w/scarring
• sulfated chains carry a - charge which increases water retention/hydration properties of the cornea
• attract Na+ and pulls in H20

• intact epith. sectretes cytokine (TGF-beta2) that inhibits type 1 collagenase production by keratocytes
• regenerating epith. secretes cytokine that stimulates type 1 collagenase production, also secretes MMP-9 which degrades BM

• abnormal KS synthesis=closer spaced fibrils and thinned cornea

• aka corneal fibroblasts
• produce collagen and proteoglycans
• maintain and repair matrix organization
• can be placed into randomly arranged collagen fibrils and move around to effect ll organization
• cannot reproduce original arrangement of fibrils

• types 1,3,5,6,7 collagen  (decreased type 1)
• acellular
• non-ll inerveaving fibrils

• anchoring fibril (type 7) link hemidesmosome to anchoring plaques (laminin) in stroma

• secretes BM
• many mitochondria
• cells are hexagonal
• gap jxns and macula occludens(desmosomes)
• NO hemidesmosomes or zonula occludens
• cells migrate and expand to fill gaps from cell loss
• repair results in polymegathism and pleomorphism

• variabilit in cell size
• indicates a greater coefficient of variation (CV)

• degree of uniformity
• SD of mean cell area/mean cell area

• long term hypoxia>increase arachodonic acid metabolites synthesized by cytochrome P-450>lead to inflamm. response and inhibition of pump
• not reversible

• can be seen in DM due to altered cell volume regulation due to osmotic effects of sorbitol, myoinositol decreases, inhibits pumps
• keratoplasty=see both for 6 months
• cataract surgery=pleomorphism for about 6 months
• keratoconus=pliomorphism and bowmans layer will disappear

• BM secreted by endothelium
• ant. banded layer=type 4 and 8
• post. unbanded layer contains laminin and grows with age
• no hemidesmosmes but fibronectin adhesion to endo.

• unusual post. descemets banding with epith. like characteristics

• endo. secretes abnormal descemets

• aging with ^ guttata
• endo thining and decreased pump
• edema
• results in poor vision
• Sequelai of Fuch's dystrophy is worse yet

• intact descemets after ulcerated epi/stroma
• aq. pressure forces membrane ant. to protrude like blister

• normal findings of descemets
• identical to guttata
• common in elderly and CL weareers
• bulge in descemets
• usually in periphery

• in palisades of vogt in perlimbal conj.
• produce basal cells
• wound healing rates greater near limbus
• unlimited mitosis
• asymmetric cell division and low initial mitotic rate
• 1 new cell remains a stem cell, 1 defferentiates into a transit cell which becomes a post mitotic cell (PMC) then terminally differentiated cells (TDC).

• latent phase (4-8hr)
• PMN invasion
• lose hemidesmosomes from edge, desmosomes remain
• membrane filopodia and lamellipodia
• fibronectin layed on BM w/in 1 hr.

• cell migration/adhesion (24-36hr)
• inlammatory response
• actin/filopodia/lamellpodia assembly
• vinculin, tenascin, talin produced
• cells increase volume and begin to migrate
• hemidesmosomes begin to establish

• adhesion/proliferation (36hr on)
• activation of limbal stem cells
• proliferation to establish full thickness
• fibronectin disappears
• re-innervation

vinculin

• cytoplasmic protein in focal adhesion plaques
• links actin to talin
• found in cells at leading edge of migration in epith. healing
• promotes adhesion to BM before hemi-d
• actin=stress fiber, contract and pull cell toward leading edge of wound
• talin=cell membrane protein, linked to inegrin=cell to ECM adhesion protein

• appears immediately after injury beneath regenerating epith.
• aids the vinculing-talin-integrin complex

• glycoprotein produced early in healing by fibroblasts
• prevents prolonged fibronectin adhesion
• promotes cont. cell migration thus acc. epith. closure

• scarring after bowmans
• rebuilt with type 3 which increases hydration and results in a weaker tissue
• slower healing than epith.
• delayed by inflamm. (steroids and NSAIDS supress this)
• aided by groth factors and cytokins
• interleukin-1 plays role in killing keratocytes intially
• repopulation in 2-3 days by activated myofibroblast which are initiated by TGF-B

• autologous serum
• activating/inhibiting certain cytokines
• therapeutic CL and tarsorrhaphy(suturing eye shut)
• lessen mechanical stress of lid windshield wiper action

• heals via expansion and migration
• 1. increases thickness, decrease pump, covered by 3d
• 2. decrease thickness and intact monolaye 4-7d
• 3. normal pump and barrier, remodeling complete 8-30d
• breaks in endo and descemets are filled by stromal collagen

• pressure at which swelling occurs (50)

• deplets glycogen
• anaerobic pthwy=less energy for cell (2 instead of 38)
• ^lactic acid=edema
• lactic acid can't pass epith., moves post. overrides effort to prevent swelling by endo bicarbonate ion pump

• stromal plexus=serves central cornea, mid 1/3 stroma to bowmans
• subepithelial plexus=in ant. stroma beneath bowmans
• conj. plexus=at limbus and feeds peripheral epith.
• descemets and endo. are not innervated and post. stroma is minimally if at all

• peptides that play a role in wound healing

• inhibit epith. wound healing if over stimulated
• pthwy=sup. cervical ganglion to stromal and subepithelial plexi
• roles in maintaining health and normal metabolism, collagen production, cl- transport, mitosis, migration of basal cells

• ulceration due to nerve damage
• loss of sensitivity leads to mechanical damage
• decreased reflex tear production

• activates GMP which has importance in growth and healing
• ACh regulation of protein kinase synthesis and intracellular Ca++

• 2 phases=degeneration(1st 48hrs) then remodeling(7-21d)
• limbal damage takes longer to repair

• difference b/n tear and stoma measured E-potential as well as an indirect measure of ion flow/comm. b/n cell layers
• requires pumps and jxns.
• controls cell volume=maintain neg. intracellular potential
• 25-40mV
• maintained primarily by Na+ and Cl-

• drug that blocks NaKATPase pump

• net mvmnt post. to aq.
• like to go to stroma b/c of neg. charge on GAG's
• highest in stroma

• higher in epith.
• NaKATPase pump pumps 3 Na+ from epith. to stroma and 2 K+ from stroma to epith.

• net mvmnt. ant. to tears
• mover from stroma to epith. by cotransport with Na+
• greatest in tears then Aq. the stroma

• cornea swells at low temp.

• higher ACTIVE conc. of Na+ in aq. than stroma
• osmotic grad. favors dehydration despite Na+ conc. being higher in stroma
• due to some stromal Na+ being bound to GAG

• maintain pump fxn or cells will swell and vacuolize and maintain jxns

• change in n

maurice's lattice theory

• perfect equal spacing of fibrils
• scattered light is suppressed by dest. int. resulting in transparency
• spacing>wl=more scatter is supp. by dest. int.
• this isn't true cause fibril spacing is small compared to wl of light

• average spacing is important
• average n must occur w/in every 200 nm or ^ scatter

• side chains of keratin sulfate
• may be responsible for maintaing corneal transparency

• inherited disorders that may result of abnormal cellular metabolism, usually bilateral, symm., w/out inlamm. and neovasc.

• autosomal dominant
• microfibrillar deposits result in corneal opacification
• due to altered proteoglycan metabolism or phspholipid metabolism

• stromal disorder due to acc. of amyloid

• heterogenous recessive
• due to abnormal keratan sulfate synthesis

• proteoglycans are responsible for the maintenance of the regular spacing and packing of the collagen fibrils, which is the basis of corneal transparency
• stromal dystrophies result in closer spacing of the collagen fibrils
• hydration of the stroma is involved with corneal transparency, more water=less transparent, decreases n and increases dist. b/n fibrils

• corneal thinning due to localized areas of corneal drying and evaporation
• persistence of one suggests that there may be a decrease in stromal flow when stromal hydration is abnormal in addition to the lateral flow of tears