It could be Orochimaru. He is known for his devious ways and might manipulate Naruto into believing false things about the ninja world.
The Akatsuki could be the cause. They are a group of powerful and often morally ambiguous characters. If they manage to capture Naruto and brainwash him, or if they make him question the Leaf Village's motives and actions through their own twisted logic, Naruto would definitely lose his way.
A new, unknown villain could be the cause. This villain might have a special power related to mind control or mental manipulation. They target Naruto because of his status as a hero in the ninja world. By making Naruto lose his mind, they could throw the entire ninja world into chaos.
In this fanfiction, Naruto could lose his way by being separated from his friends for a long time. Without their support and guidance, he may make wrong decisions. For example, he could be tricked into working for an enemy who disguises as a friend in need. This would lead him down a path where he gradually loses sight of his original goals and the positive ninja way he once followed.
There's also the possibility that it's an accidental injury caused by one of Naruto's friends during a training session gone wrong. For example, Sasuke could accidentally unleash a jutsu that hits Naruto's eye while they are sparring.
It could be Sasuke. If Sasuke has some sort of newfound connection with Naruto and it causes Naruto to shift his focus away from Sakura, then Sasuke would be the cause. For example, if Sasuke and Naruto team up for a powerful mission and their bond deepens in a way that makes Naruto neglect his relationship with Sakura.
It could be Danzo. He was always power - hungry and had his own ideas about what was best for the village. He might see Naruto as a threat and find a way to take away his birthright.
Perhaps he was in a battle against a very strong enemy. The enemy might have used a special attack that specifically targeted his eyes, like a genjutsu that damaged his optic nerves when he broke free from it.
Arthur could be the cause. He often bosses Merlin around and doesn't fully understand Merlin's capabilities. His constant demands and lack of respect for Merlin's intelligence might push Merlin to the edge. For instance, when Arthur makes Merlin do dangerous and pointless tasks without any regard for his safety.
Maybe he was protecting someone in Wave. He's always the self - sacrificing type, so he could have put himself in harm's way to save a villager or a friend.
Well, in such a fanfiction, Naruto might find himself in a strange new land where he has no idea how to get back home. Maybe he loses his memories and has to start from scratch to figure out who he is and what his purpose is.
One possible reason could be an enemy attack. A powerful and malicious foe might target Naruto's family to get back at him, and his wife could unfortunately become a casualty in the battle.