Abstract Title

Effect of BAMBI expression on intraocular pressure and aqueous humor outflow facility in mice

RAD Assignment Number

911

Presenter Name

Humberto Hernandez

Abstract

Purpose: Elevated intraocular pressure (IOP) is an important risk factor in the development of glaucoma. TGFβ2 is well known to be involved in regulating both the extracellular matrix in the trabecular meshwork (TM) as well as ocular hypertension. BAMBI (BMP and activin membrane-bound inhibitor), a TGF-β pseudoreceptor, has been shown to be a negative regulator of TGF-β2. However, the role of BAMBI in regulating IOP is unknown. We investigated whether knockdown of BAMBI results in ocular hypertension in mice due to uninhibited TGFβ2 signaling.

Methods: B6;129S1-Bambitm1Jian/J mice were injected intravitreally with 2.5x107 pfu of either Ad5.TGFβ2 (n=10), Ad5.Cre (n=9), or Ad5.TGFβ2 + Ad5.Cre (n=10), in one eye of each animal. The contralateral uninjected eyes were used as negative controls. IOP was measured using a TonoLab rebound tonometer. Aqueous humor outflow facility was assessed using a constant flow infusion method. Student’s t-test was used to compare between vector-treated and control uninjected eyes.

Results: Injection with either Ad5.Cre, Ad5.TGFβ2, or Ad5.TGFβ2 + Ad5.Cre each induced ocular hypertension starting at day 7 post-injection and maintained significant IOP elevation throughout the 56 day time course compared to uninjected control eyes (p

Conclusions: Here we show for the first time that conditional knockdown of BAMBI in the TM with Ad5.Cre induces ocular hypertension by reducing aqueous humor outflow facility. These data further explain the mechanisms involved in the development of glaucomatous TM damage and provide potential new targets to lower IOP.

Presentation Type

Poster

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Effect of BAMBI expression on intraocular pressure and aqueous humor outflow facility in mice

Purpose: Elevated intraocular pressure (IOP) is an important risk factor in the development of glaucoma. TGFβ2 is well known to be involved in regulating both the extracellular matrix in the trabecular meshwork (TM) as well as ocular hypertension. BAMBI (BMP and activin membrane-bound inhibitor), a TGF-β pseudoreceptor, has been shown to be a negative regulator of TGF-β2. However, the role of BAMBI in regulating IOP is unknown. We investigated whether knockdown of BAMBI results in ocular hypertension in mice due to uninhibited TGFβ2 signaling.

Methods: B6;129S1-Bambitm1Jian/J mice were injected intravitreally with 2.5x107 pfu of either Ad5.TGFβ2 (n=10), Ad5.Cre (n=9), or Ad5.TGFβ2 + Ad5.Cre (n=10), in one eye of each animal. The contralateral uninjected eyes were used as negative controls. IOP was measured using a TonoLab rebound tonometer. Aqueous humor outflow facility was assessed using a constant flow infusion method. Student’s t-test was used to compare between vector-treated and control uninjected eyes.

Results: Injection with either Ad5.Cre, Ad5.TGFβ2, or Ad5.TGFβ2 + Ad5.Cre each induced ocular hypertension starting at day 7 post-injection and maintained significant IOP elevation throughout the 56 day time course compared to uninjected control eyes (p

Conclusions: Here we show for the first time that conditional knockdown of BAMBI in the TM with Ad5.Cre induces ocular hypertension by reducing aqueous humor outflow facility. These data further explain the mechanisms involved in the development of glaucomatous TM damage and provide potential new targets to lower IOP.