*2.2. Mice*

All mice utilized in this study were housed in the Cole Eye Institute vivarium under approved Institutional Animal Care and Use Committee (IACUC) protocols. All procedures on the mice were in accordance with ARVO statement for the Use of Animals in Ophthalmic and Vision Research and conformed to the National Institutes of Health Guide for the Care and Use of Animals in Research and to the ARVO statement for the use of animals in ophthalmic and vision research. Timp3+/S179C mice were generated in the laboratory of Dr. Bernhard Weber using site-directed mutagenesis and homologous recombination in embryonic stem (ES) cells to generate mutant ES cells carrying the *Timp3S179C* allele. Heterozygous breeding of Timp3+/S179C [33] produced homozygous Timp3S179C/S179C mice and age-matched littermate controls in a C57BL6 background. Similarly, heterozygous Timp3+/- mice [34] were bred to generate Timp3-/- knockouts and TIMP3+/+ littermate controls. Eyes were enucleated following euthanasia and fresh frozen in tissue-plus optical cutting temperature embedding medium (Scigen, #4583) for sectioning and histology. Blood samples were collected via cardiac puncture and plasma prepared via standard protocols.

### *2.3. Hyaluronan Enzyme-Linked Immunosorbent Assay (ELISA)*

Plasma from human patients with and without AMD and from SFD mouse models were measured for HA contents by solid-phase sandwich ELISA in 96-well plates (Costar, #9018) using the Hyaluronan Duo-Set ELISA kit (R&D Systems, #DY3614-05).
