Rock Band 3's Pro Guitar is Lefty Compatible

Lefty mode for the Pro Guitar (the guitar controller by Mad Catz with 102 fret buttons) is available for Rock Band 3 and is as simple as switching modes in the menu.

This is what was stated in the email sent by Harmonix to Kotaku:

"With regards to gameplay, lefty flip for the Pro guitar will worklike any other controller. Just select 'lefty flip' in your menu, turn your guitar around and get back to rocking. Pro gameplay on screen will adjust accordingly, just as traditional Rock Band gameplay has in the past."

Players with older Rock Band guitars will not be able to play the game's Pro Guitar mode. Players with only those guitars will be able to play the game's standard guitar mode in either orientation.

Source: Kotaku