| Persistent hyperplastic primary vitreous (PHPV) is a specific retardation of ocular development in which the fetal hyaloid artery and associated vasculature fail to regress prior to birth. The anterior form of this condition can present with an early-onset cataract, a retrolental fibrovascular mass, and a break in the posterior surface of the lens capsule. These ocular signs can cause decreased visual acuity. Certain matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are known to remodel the lens and basement membranes throughout the body. I hypothesize that the break in the posterior lens capsule occurs prior to the formation of the cataract, and that the break is the result of the enzymatic action of MMPs, which are present in the retrolental mass.;To study these hypotheses, I shall run several experiments. First, I'll use light microscopy to chronicle the time course over which the retrolental mass approaches the posterior capsule, the posterior capsule break occurs, and lenticular degeneration becomes evident. Using transmission electron microscopy (TEM), I shall look at the posterior lens capsule in cross-section to more accurately plot the time period over which the ultrastructure loses its organization and solvency. To follow up on this, I shall use immuno-histochemistry and Western blotting to determine which protein components of the capsule are affected. Reverse transcriptase PCR (RT-PCR) will be performed to determine if a defect in the mRNA of the lens epithelium is involved. To check if the protein destruction is caused by high MMP levels or low TIMP levels, immunohistochemistry and Western blots will be used, with RT-PCR of the retrolental mass and lens epithelial cells, to confirm the source of the enzymes. Knock-out mice lacking the enzyme in question will be bred to determine whether it is necessary to cause signs of PHPV, and mice with an retrobulbar MMP-expressing retinoblastoma cell mass to determine if the expression of the enzyme is sufficient to produce capsular break, all else being the same.;These experiments should help in our understanding of PHPV and the unusual posterior lens capsule break that presents in that condition. Depending upon the information gleaned, it may be possible to develop a treatment for infants with PHPV to prevent cataracts and the visual acuity decrease that corresponds to it. |
