[Skip to Content]
[Skip to Content Landing]
Article
January 1995

Immunohistochemical Localization of Fibrillin in Human Ocular TissuesRelevance to the Marfan Syndrome

Author Affiliations

From The Johns Hopkins Center for Hereditary Eye Diseases (Drs Wheatley, Traboulsi, Flowers, and Maumenee), the Keratorefractive (Dr Azar) and Cornea (Dr Azar) Services, and the Ocular Immunology Laboratory (Dr Whittum-Hudson), Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Md; and the Department of Human Genetics (Dr Pyeritz), Allegheny-Singer Research Institute, Pittsburgh, Pa.

Arch Ophthalmol. 1995;113(1):103-109. doi:10.1001/archopht.1995.01100010105028
Abstract

Objective:  To better understand the ocular manifestations of the Marfan syndrome, we investigated the distribution of fibrillin in normal human ocular tissues. Fibrillin, a microfibrillar glycoprotein component of the extracellular matrix, has been found to be the defective gene product in the Marfan syndrome.

Methods:  Frozen sections from seven pairs of normal eyes were stained with mouse anti—human fibrillin antibodies using the avidin-biotin immunoperoxidase technique.

Results:  In the anterior segment, the following exhibited positive staining for fibrillin: the lens capsule and zonules; connective tissues of the iris, ciliary body, ciliary processes, and conjunctiva; and the basement membrane regions of the corneal epithelium and endothelium of Schlemm's canal. Posteriorly, fibrillin localized to the lamina cribrosa, sclera, choroid, and Bruch's membrane.

Conclusions:  Fibrillin is widely distributed in ocular connective tissues. The implications of defects in these tissues and the resultant ocular abnormalities in the Marfan syndrome such as ectopia lentis and glaucoma are discussed.

References
1.
Sakai LY, Keene DR, Engvall E.  Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils . J Cell Biol . 1986;103:2499-2509.Article
2.
Magenis RE, Maslen CL, Smith L, Allen L, Sakai LY.  Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1 . Genomics . 1991;11:346-351.Article
3.
Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, Peltonen L.  Location on chromosome 15 of the gene defect causing Marfan syndrome . N Engl J Med . 1990;323:935-939.Article
4.
Dietz HC, Pyeritz RE, Hall BD, et al.  The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3 . Genomics . 1991;9:355-361.Article
5.
Lee B, Godfrey M, Vitale E, et al.  Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes . Nature . 1991;352:330-334.Article
6.
Dietz HC, Cutting GR, Pyeritz RE, et al.  Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene . Nature . 1991;352:337-339.Article
7.
Sarfarazi M, Tsipouras P, Del Mastro R, et al.  A linkage map of 10 loci flanking the Marfan syndrome locus on 15q: results of an international consortium study . J Med Genet . 1992;29:75-80.Article
8.
Tsipouras P, Del Mastro R, Sarfarazi M, et al.  Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5: the International Marfan Syndrome Collaborative Study . N Engl J Med . 1992;326:905-909.Article
9.
Raghunath M, Superti-Furga A, Godfrey M, Steinmann B.  Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts . Hum Genet . 1993;90:511-515.Article
10.
Hollister DW, Godfrey M, Sakai LY, Pyeritz RE.  Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome . N Engl J Med . 1990;323:152-159.Article
11.
Milewicz DM, Pyeritz RE, Crawford ES, Byers PH.  Marfan syndrome: defective synthesis, secretion, and extracellular matrix formation of fibrillin by cultured dermal fibroblasts . J Clin Invest . 1992;89:79-86.Article
12.
Godfrey M.  The Marfan syndrome . In: Beighton P, ed. McKusick's Heritable Disorders of Connective Tissue . 5th ed. St Louis, Mo: CV Mosby Co; 1993:51-135.
13.
Maumenee IH.  The eye in Marfan syndrome . Trans Am Ophthalmol Soc . 1981;79:684-733.
14.
Izquierdo NJ, Traboulsi El, Enger C, Maumenee IH.  Glaucoma in the Marfan syndrome . Trans Am Ophthalmol Soc . 1992;90:111-122.
15.
Morrison JC, Jerdan JA, Dorman ME, Quigley HA.  Structural proteins of the neonatal and adult lamina cribrosa . Arch Ophthalmol . 1989;107:1220-1224.Article
16.
Wallace RN, Streeten BW, Hanna RB.  Rotary shadowing of elastic system microfibrils in the ocular zonule, vitreous, and ligamentum nuchae . Curr Eye Res . 1991;10:99-109.Article
17.
Keene DR, Maddox BK, Kuo HJ, Sakai LY, Glanville RW.  Extraction of extendable beaded structures and their identification as fibrillin-containing extracellular matrix microfibrils . J Histochem Cytochem . 1991;39:441-449.Article
18.
Azar DT, Gipson IK.  Immunolocalization of fibrillin and type VII collagen in keratoconus corneas . Invest Ophthalmol Vis Sci . 1990;31( (March suppl) ):100. Abstract 493.
19.
Zaidi TS, Hasan A, Baum J, Panjwani N.  Localization of fibrillin in normal human and bovine corneas . Invest Ophthalmol Vis Sci . 1991;32( (March suppl) ): 875. Abstract 1017.
20.
Dark AJ, Streeten BW.  Precapsular film on the aging human lens: precursor of pseudoexfoliation? Br J Ophthalmol . 1990;74:717-722.Article
21.
Dahlback K, Ljungquist A, Lofberg H, Dahlback B, Engvall E, Sakai LY.  Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis . J Invest Dermatol . 1990;94:284-291.Article
22.
Whittum-Hudson JA, Pepose JS.  Immunologic modulation of virus-induced pathology in a murine model of acute herpetic retinal necrosis . Invest Ophthalmol Vis Sci . 1987;28:1541-1548.
23.
Dvorak-Theobald G.  Histologic eye findings in arachnodactyly . Am J Ophthalmol . 1941;24:1132-1137.
24.
Reeh MJ, Lehman WL.  Marfan's syndrome (arachnodactyly) with ectopia lentis . Trans Am Acad Ophthalmol Otolaryngol . 1954;58:212-216.
25.
Wachtel JG.  The ocular pathology of Marfan's syndrome . Arch Ophthalmol . 1966;76:512-522.Article
26.
Allen RA, Straatsma BR, Apt L, Hall MO.  Ocular manifestations of the Marfan syndrome . Trans Am Acad Ophthalmol Otolaryngol . 1967;71:18-38.
27.
Ramsey MS, Fine BS, Shields JA, Yanoff M.  The Marfan syndrome: a histopathologic study of ocular findings . Am J Ophthalmol . 1973;76:102-116.
28.
Farnsworth PN, Burke P, Dotto ME, Cinotti AA.  Ultrastructural abnormalities in a Marfan's syndrome lens . Arch Ophthalmol . 1977;95:1601-1606.Article
29.
Briglin CA, Li Z-Y, Streeten BW.  Cultured lens epithelial cells synthesize matrix immunopositive for elastic microfibrillar proteins, including fibrillin and a zonular peptide . Invest Ophthalmol Vis Sci . 1991;32( (March suppl) ):777. Abstract 543.
30.
Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye . Philadelphia, Pa: WB Saunders Co; 1971.
31.
Marshall GE, Konstas AG, Bechrakis NE, Lee WR.  An immunoelectron microscope study of the aged human lens capsule . Exp Eye Res . 1992;54:393-401.Article
32.
Porte A, Stoeckel ME, Brini A.  Sur l'insertion des fibres zonulaires sur la capsule du cristallin humain . Arch Ophthalmol . 1971;31:445-454.
33.
Burian HM, Allen L.  Histologic study of the chamber angle of patients with Marfan's syndrome . Arch Ophthalmol . 1961;65:323-333.Article
34.
Kielty CM, Berry L, Whittaker SP, Grant ME, Shuttleworth CA.  Microfibrillar assemblies of foetal bovine skin: developmental expression and relative abundance of type VI collagen and fibrillin . Matrix . 1993;13:103-112.Article
35.
Kielty CM, Whittaker SP, Grant ME, Shuttleworth CA.  Attachment of human vascular smooth muscle cells to intact microfibrillar assemblies of collagen VI and fibrillin . J Cell Sci . 1992;103( (pt 2) ):445-451.
36.
Gipson IK.  The epithelial basement membrane zone of the limbus . Eye . 1989;3:132-140.Article
×