Special Senses System

Eye, Vitreous - Fibrosis

Narrative

Comment:

Various insults to the vitreous (penetrating injury, inflammation, etc.) can result in reactive vascularization and organization with proliferation of vitreal fibrous connective tissue (vitreal scar or fibrous membrane formation). In early fibrosis, loose fibrous connective tissue fills the vitreous space (Figure 1 and Figure 2) between the lens and retina. More advanced fibrosis (Figure 3 and Figure 4) is characterized by dense sheets of mature fibrous tissue that replace the normal vitreous. Vitreous fibrosis is often associated with chronic inflammation and/or pigmented macrophage accumulations (Figure 1, Figure 2, Figure 3, and Figure 4).

Reactive retinal pigment epithelium (RPE) cells may migrate transretinally into the vitreous (Figure 5) and spreading along the inner surface of the retina. Such migrant RPE cells can undergo fibrous metaplasia (epithelial-to-mesenchymal transition) into fibroblast-like cells and participate in the formation of abnormal vitreal fibrous tissue, including fibrous membranes on the surface of the retina and other posterior ocular structures. Other cells that participate in development of vitreal fibrosis include activated resident vitreal hyalocytes, retinal Müller cells and astrocytes, immigrant macrophages, and scleral fibroblasts. Cartilaginous or osseous metaplasia can occasionally form in late-stage vitreal fibrosis (Figure 6).

Recommendations:

Vitreous fibrosis should be diagnosed and assigned a severity grade. If pertinent to the characterization of a treatment-related effect, the morphology and distribution of the fibrous tissue (e.g., epiretinal membranes) should be described in the narrative. The pathologist should exercise judgment in deciding whether to diagnose only vitreal inflammation or vitreal fibrosis in a given animal, or whether to diagnose both. Features such as RPE cell migration and cartilaginous and osseous metaplasia should not be diagnosed separately, though they can be described in the pathology narrative.

References:

Bringmann A, Wiedemann, P. 2009. Involvement of Müller glial cells in epiretinal membrane formation. Graefes Arch Clin Exp Ophthalmol 247:865-883.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/19415318

Frame SR, Slone TW. 1966. Nonneoplastic and neoplastic changes in the eye. In: Pathobiology of the Aging Mouse, Vol 2 (Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM, eds). ILSI Press, Washington, DC, 97-103.

Hogg PA, Grierson I, Hiscott P. 2002. Direct comparison of the migration of three cell types involved in epiretinal membrane formation. Invest Ophthalmol Vis Sci 43:2749-2757.

Full Text: http://tpx.sagepub.com/content/35/2/252.full

Mecklenburg L, Schraermeyer U. 2007. An overview on the toxic morphological changes in the retinal pigment epithelium after systemic compound administration. Toxicol Pathol 35:252-267.

Full Text: http://tpx.sagepub.com/content/35/2/252.full

National Toxicology Program. 1992. NTP TR-407. Toxicology and Carcinogenesis Studies of C.I. Pigment Red 3 (CAS No. 2425-85-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/7694

National Toxicology Program. 1992. NTP TR-415. Toxicology and Carcinogenesis Studies of Polysorbate 80 (CAS No. 9005-65-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/7710

National Toxicology Program. 2001. NTP TR-501. Toxicology and Carcinogenesis Studies of p, p'-Dichlorodiphenyl Sulfone (CAS No. 80-07-9) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/14880

Saika S, Kono-Saika S, Ohnishi Y, Sato M, Muragaki Y, Ooshima A, Flanders KC, Yoo J, Anzano M, Liu C-Y, Kao W W-Y, Roberts AB. 2004. Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. Am J Pathol 164:651-663.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/14742269

Smith RS. 2002. Choroid, lens, and vitreous. In: Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods (Smith RS, John SWM, Nishina PM, Sundberg JP, eds). CRC Press Boca Raton, FL, 161-193.

Smith RS, Hawes NL, Chang B, Nishina PM. 2002. Retina. In: Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods (Smith RS, John SWM, Nishina PM, Sundberg JP, eds). CRC Press, Boca Raton, FL, 195-225.

Yoshitomi K, Boorman GA. 1990. Eye and associated glands. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, CA, 239-260.

Abstract: https://www.ncbi.nlm.nih.gov/nlmcatalog/9002563

All Images

Eye, Vitreous - Fibrosis in a male F344/N rat from a chronic study. There is loose fibrous connective tissue (asterisk) in the vitreous space between a cataractous lens (L) and a detached, degenerate retina (R).

Eye, Vitreous - Fibrosis in a male F344/N rat from a chronic study (higher magnification of Figure 1). There is loose fibrous connective tissue (asterisk) with space scattered pigmented macrophages (arrow) in the vitreous; L = cataractous lens.

Eye, Vitreous - Fibrosis in a female F344/N rat from a chronic study. There is advanced fibrosis in the vitreous space characterized by dense fibrous connective tissue (asterisk) with chronic inflammation (arrow); L = cataractous lens, R = detached, degenerate retina.

Eye, Vitreous - Fibrosis in a female F344/N rat from a chronic study (higher magnification of Figure 3). The advanced fibrosis is characterized by dense fibrous connective tissue (asterisk) in the vitreous space with chronic inflammation (arrow); L = cataractous lens, R = detached degenerate retina.

Eye, Vitreous - Fibrosis in a female F344/N rat from a chronic study. There is fibrosis (asterisk) and infiltration by migrating reactive epithelial cells (arrow) from the retinal pigment epithelium (arrowhead) in the vitreous space in the eye; R = detached and degenerate retina.

Eye, Vitreous - Fibrosis in a male B6C3F1 mouse from a chronic study. Area of dense, mature fibrous connective tissue in the vitreous (V) and focal cartilaginous metaplasia (arrow); S = sclera.

Authors and Reviewers

Author

Margarita M. Gruebbel, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Ruth E. Hurley, DVM, PHD, DACVP
Senior Veterinary Pathologist
Huntingdon Life Sciences
North Brunswick, NJ

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC