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The former schoolteacher beat Pacquiao in a unanimous 12-round points decision in Brisbane in 2017, seen as one of the greatest moments in Australian sport.
Pacquiao pulled out of a planned rematch later that year, with Horn going on to win three more fights while losing to Australian Michael Zerafa and American Terence Crawford.
His last bout was a defeat at the hands of current interim WBO super welterweight champion Tim Tszyu nearly three years ago, but he had never officially retired.
Horn, 35, told the Brisbane Courier-Mail newspaper he had been offered a big-money deal for a comeback bout with Zerafa but turned it down.
"I could have taken $1 million for another fight, but my health is more important than wealth," Horn said on the sixth anniversary of the Pacquiao fight.
"To be honest, I've had my concerns. I've had some issues with my memory.
"I've had some tests done on my brain and I was told if I kept going there was a high potential risk of things getting worse and my brain suffering more."
Horn finished his career with a 20-3-1 record.
