Materials and methods for the treatment of pathological neovascularization in the eye

A method of reducing or preventing ocular neovascularization in a subject, wherein the method consists of administering, into one or more target ocular tissues of the subject, said target ocular tissues selected from the group consisting of the retinal, choroidal and corneal ocular compartments, an expression vector comprising a transgene encoding a therapeutic molecule, wherein the transgene is operably linked to an ocular-specific promoter and becomes hypoxia-responsive when said ocular-specific promoter is placed under the control of a hypoxia responsive element and selectively drives gene expression in retinal cells, retinal pigment epithelial cells, Muller cells, choroid cells and combinations thereof;

• wherein said hypoxia responsive element is a hypoxia regulated silencing element (HRSE) including at least one hypoxia responsive element (HRE) sequence which upregulates gene expression under hypoxia or inflammation and at least one neuron-restrictive silencer element (NRSE) sequence which silences gene expression under normoxia,
• wherein the ocular-specific promoter selectively drives gene expression in the ocular tissue having, or at risk of developing, neovascularization,
• wherein the hypoxia-responsive element upregulates gene expression under hypoxia or inflammation but not under normoxia,
• whereby ocular neovascularization is reduced or prevented.