Connective Tissue - Week 4 Flashcards
Provide 2 examples of heritable C.T (conn tissue) disorders:
Stickler syndrome - vitreous changes
Marfan syndrome - ectopic lens
Provide 1 example of an autoimmune CT disorder:
Scleritis - sclera like necrosis
Which CT disorder can be characterised by scleral thinning?
High myopia
What can the presence of abnormal fibrillar collagen molecules cause? (3)
1) delay fibril formation
2) reduce total amount of collagen incorporated into the fibrils
3) alter the morphology of the fibrils
How may alterations in amino acid content or spacing affect collagen? (3 things affected)
Affect collagen:
- structure
- stability
- biological performance
Hydroxyproline is a major component of the protein collagen. What is it important for?
The sharp twisting of the collagen helix, which is temperature dependent
What results from the absence of Hydroxyproline?
Reduced Thermal stability of collagen triple helix
Compare the % of helix content between normal collagen and collagen without Hydroxyproline at 40 degrees celsius
At 40 degrees,
Normal collagen = 100% helix content
Without Hydroxyproline = ~10%
What do changes in collagen ECM components affect? How can these changes occur?
Collagen structure
Can be genetic or environmentally derived
What can mutation in a constituent single protein molecule do?
Has a profound effect on molecular complex and tissues
What type of collagen interaction is important for regulating fibril diameter?
Heterotypic type I/V interactions
type one/five
List the general issues that can have profound effects on collagen structure/function (5)
- presence of abnormal molecules
- altered amino acid spacing or content
- changes in ECM matrix components
- mutation in constituent single protein molecule
- altered expression in protein associated macromolecules
List the 4 ways the immune system can respond:
1/ Defend successfully
2/ Autoimmunity - fail to distinguish self vs non-self
3/ Hypersensitivity - excess response
4/ immune deficiency - inadequate/absent response
List the 5 main components of the immune system response
- recognition
- specificity
- antibody production
- cell-mediated reactions
- memory
What is Sjögren’s syndrome and what occurs in it?
Autoimmune disease of connective tissue
Involves t-cell infiltration of lacrimal gland
leads to inability to secrete saliva or tears
How is Stickler’s syndrome inherited?
Autosomal dominant (and newly identified recessive form)
Define arhtro-opthalmopathy. List a CT disorder that could be described this way
- an association of degenerative joint disease and eye disease
- Stickler Syndrome
What are the 5 subgroups of ocular and systemic manifestations that result from Stickler Syndrome?
Type 1 - ocular + systemic Type 2 - ocular + systemic Type 3 - systemic only Type 4 - ocular + systemic; recessive (Type 5) - ocular only (similar to type 1 but w/o systemic)
What are the functional ocular consequences of Stickler Syndrome?
Ocular:
- vitreous abnormalities
- retinal degeneration/tears/breaks
- cataracts
- glaucoma (open angle)
- high myopia
What are the functional systemic consequences of Stickler Syndrome?
Systemic:
- skull, joint abnormalities
- hearing loss
- cleft palate
- heart problems
What are the identified mutations in Stickler syndrome types (4)?
Type 1 - COL2A1
Type 2 - COL11A1
Type 3 - COL11A2
Recessive - COL9A1 and COL9A2
What local clinical manifestations in the eye arise from the first 4 types of Stickler Syndrome?
Type 1 - sometimes vitreous manifestations only, sheet-like vitreous opacities or vitreous hypoplasia
Type 2 - Bead-like vitreous opacities or vitreous hypoplasisa
Type 3 - No ocular phenotype
(Type 4) Recessive - premature vitreous degen.
What type of anomalies are the following types of Stickler Syndrome: 1, 2 and 4?
Type 1 - membranous vitreal anomaly
Type 2 - beaded vitreal anomaly
Type 4 - premature vitreous degen.
Which type of Stickler Syndrome presents with a loss of collagen type IX? Is this also a feature of age-related vitreous changes?
Type 4, yes
T/F: Vitreoretinal adhesions are a feature of age-related vitreous changes but NOT Stickler type 4
False. It is a feature of both
What mutations causes Marfan syndrome?
Mutation in fibrillin-1 gene (80% of cases) new mutations (25% of cases)
Describe the pattern of inheritance for Marfan Syndrome
Autosomal dominant with high penetrance
Explain the major ocular complication of Marfan Syndrome.
‘Ectopia Lentis’ - i.e. the lens is displaced
Clinical pathology of Marfan syndrome (4)
- lens displaced
- flat cornea
- increased axial length of globe
- hypoplastic iris or hypoplastic cil. muscle causing decreased miosis (i.e. underdevelopment of cil. mus./iris)
In Marfan syndrome, where does lens displacement occur?
Usually superiotemporally
List the functional consequences of Scleritis
In severe cases:
- thickened sclera
- intraocular sequelae incl. retinal detachment
- gluacoma
In very severe cases:
- necrosis + scleral perforation
- intraocular sequelae incl. infection
T/F: The fibres MUST have a problem/mutation in gene encoding alpha sub units to cause CT disorder
False
What is Lumican?
A small proteoglycan present in the corneal stroma
What can a lack of lumican result in?
- larger fibril diameters
- disorganised fibril spacing
- corneal clouding
What is a frequent comorbidity of Scleritis? And is it painful? How long until it resolves
Episcleritis. Causes mild discomfort without pain. Usually resolves within 2 weeks
How does impaired fibrillin-1 affect the lens zonules?
Weakens them
List the 4 different presentations of sceleritis:
- Acute
- Nodular
- Necrotising with inflammation
- Necrotising without inflammation
Is high myopia considered a CT disorder?
Yes
How many diopters is high myopia?
More than 6
How does high myopia affect axial length?
Increased axial length
How does high myopia affect risk of chorioretinal degeneration and retinal detachment?
Increases risk for both
What happens to the sclera in high myopia? Where does this happen?
Sclera thins dramatically at the posterior pole
Name a possible genetic explanation for high myopia?
Mutation in SCO2 gene
What is the role of the SCO2 gene?
Helps metabolise copper and thus regulates O2 in the eye
Explain the functional significance of high myopia? (4)
- reduced tensile strength of sclera
- major effect at posterior pole
- increased rate of eye growth under normal IOP
- feature of young eyes and myopic eyes
