Provided herein are methods for treating myocilin (MYOC) glaucoma using adeno-associated viral (AAV) vectors. In some aspects, the AAV vectors encode R-spondin 1 (RSPO1), R-spondin 2 (RSPO2), R-spondin 3 (RSPO3) or R-spondin 4 (RSPO4) and/or RNAi that targets myocilin (MYOC). In one aspect, viral particles are administered to the eye of a human subject. Viral particles encoding RSPO1, RSPO2, RSPO3 and/or RSPO4 and/or MYOC RNAi are contemplated. In some aspects, variant AAV2 particles that transduce the trabecular meshwork are provided.