There are three major highway interstates that run through Toledo. Interstate 75 (I-75) travels north-south and provides a direct route to Detroit and Cincinnati. The Ohio Turnpike carries east-west traffic on Interstate 80 and Interstate 90. The Turnpike is connected to Toledo via exits 52, 59, 64, 71, and 81. The Turnpike connects Toledo to South Bend and Chicago to the West and Cleveland to the East. In addition, there are two minor highway interstates in the area. Interstate 475 is a loop that both begins and ends on I-75 in Perrysburg and West Toledo, respectively. Interstate 280 is a spur that travels mostly through east Toledo. This highway travels over the newly constructed Veterans' Glass City Skyway which was most expensive ODOT project ever at its completion. This 400-foot (120 m) tall bridge includes a glass covered pylon, which lights up at night, adding a distinctive feature to Toledo's skyline. The Anthony Wayne Bridge, a 3,215-foot (980 m) suspension bridge crossing the Maumee River, has been a staple of Toledo's skyline for more than 70 years. It is locally known as the "High-Level Bridge."

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